Genes

17 pages, 3923 KiB

Open AccessEditor’s ChoiceArticle

Sequencing and Description of the Mitochondrial Genome of Orthopodomyia fascipes (Diptera: Culicidae)

by Fábio Silva da Silva, Bruna Laís Sena do Nascimento, Ana Cecília Ribeiro Cruz, Sandro Patroca da Silva, Carine Fortes Aragão, Daniel Damous Dias, Lucas Henrique da Silva e Silva, Lúcia Aline Moura Reis, Hanna Carolina Farias Reis, Liliane Leal das Chagas, José Wilson Rosa Jr., Durval Bertram Rodrigues Vieira, Roberto Carlos Feitosa Brandão, Daniele Barbosa de Almeida Medeiros and Joaquim Pinto Nunes Neto

Genes 2024, 15(7), 874; https://doi.org/10.3390/genes15070874 - 3 Jul 2024

Cited by 2 | Viewed by 1724

Abstract

The genus Orthopodomyia Theobald, 1904 (Diptera: Culicidae) comprises 36 wild mosquito species, with distribution largely restricted to tropical and temperate areas, most of which are not recognized as vectors of epidemiological importance due to the lack of information related to their bionomy and [...] Read more.

The genus Orthopodomyia Theobald, 1904 (Diptera: Culicidae) comprises 36 wild mosquito species, with distribution largely restricted to tropical and temperate areas, most of which are not recognized as vectors of epidemiological importance due to the lack of information related to their bionomy and involvement in the cycle transmission of infectious agents. Furthermore, their evolutionary relationships are not completely understood, reflecting the scarcity of genetic information about the genus. Therefore, in this study, we report the first complete description of the mitochondrial genome of a Neotropical species representing the genus, Orthopodomyia fascipes Coquillet, 1906, collected in the Brazilian Amazon region. Using High Throughput Sequencing, we obtained a mitochondrial sequence of 15,598 bp, with an average coverage of 418.5×, comprising 37 functional subunits and a final portion rich in A + T, corresponding to the control region. The phylogenetic analysis, using Maximum Likelihood and Bayesian Inference based on the 13 protein-coding genes, corroborated the monophyly of Culicidae and its two subfamilies, supporting the proximity between the tribes Orthopodomyiini and Mansoniini, partially disagreeing with previous studies based on the use of molecular and morphological markers. The information generated in this study contributes to a better understanding of the taxonomy and evolutionary history of the genus and other groups of Culicidae. Full article

(This article belongs to the Special Issue Genetics, Phylogeny, and Evolution of Insects)

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11 pages, 1082 KiB

Open AccessEditor’s ChoiceArticle

The Evolution of Genetic Variability at the LRRK2 Locus

by Dylan T. Guenther, Jordan Follett, Rim Amouri, Samia Ben Sassi, Faycel Hentati and Matthew J. Farrer

Genes 2024, 15(7), 878; https://doi.org/10.3390/genes15070878 - 3 Jul 2024

Cited by 2 | Viewed by 1827

Abstract

Leucine-rich repeat kinase 2 (LRRK2) c.6055G>A (p.G2019S) is a frequent cause of Parkinson’s disease (PD), accounting for >30% of Tunisian Arab-Berber patients. LRRK2 is widely expressed in the immune system and its kinase activity confers a survival advantage against infection in [...] Read more.

Leucine-rich repeat kinase 2 (LRRK2) c.6055G>A (p.G2019S) is a frequent cause of Parkinson’s disease (PD), accounting for >30% of Tunisian Arab-Berber patients. LRRK2 is widely expressed in the immune system and its kinase activity confers a survival advantage against infection in animal models. Here, we assess haplotype variability in cis and in trans of the LRRK2 c.6055G>A mutation, define the age of the pathogenic allele, explore its relationship to the age of disease onset (AOO), and provide evidence for its positive selection. Full article

(This article belongs to the Section Genes & Environments)

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14 pages, 7152 KiB

Open AccessEditor’s ChoiceArticle

Characterization and Phylogenetic Analysis of the Chloroplast Genomes of Stephania japonica var. timoriensis and Stephania japonica var. discolor

by Li-Li Wu, Ying-Min Geng and Lan-Ping Zheng

Genes 2024, 15(7), 877; https://doi.org/10.3390/genes15070877 - 3 Jul 2024

Cited by 2 | Viewed by 1351

Abstract

This study sequenced the complete chloroplast genomes of Stephania japonica var. timoriensis and Stephania japonica var. discolor using the Illumina NovaSeq and PacBio RSII platforms. Following sequencing, the genomes were assembled, annotated, comparatively analyzed, and used to construct a phylogenetic tree to explore [...] Read more.

This study sequenced the complete chloroplast genomes of Stephania japonica var. timoriensis and Stephania japonica var. discolor using the Illumina NovaSeq and PacBio RSII platforms. Following sequencing, the genomes were assembled, annotated, comparatively analyzed, and used to construct a phylogenetic tree to explore their phylogenetic positions. Results indicated that the chloroplast genomes of S. japonica var. timoriensis and S. japonica var. discolor both displayed a typical double-stranded circular tetrameric structure, measuring 157,609 and 157,748 bp in length, respectively. Each genome contained 130 annotated genes, with similar total GC content and relative codon usage patterns, showing a distinct preference for A/U at the third codon position. Simple sequence repeat analysis identified 207 and 211 repeats in S. japonica var. timoriensis and S. japonica var. discolor, respectively, primarily the A/T type. Boundary condition analysis indicated no significant expansion or contraction in the inverted repeat regions with consistent gene types and locations across both varieties. Nucleotide polymorphism analysis highlighted greater variation in the intergenic regions than in the coding sequences of Stephania chloroplast genomes. Phylogenetic analyses demonstrated that the species Stephania clustered into a distinct, well-supported clade. Notably, Stephania japonica, along with S. japonica var. discolor and S. japonica var. timoriensis, established a monophyletic lineage. Within this lineage, S. japonica and S. japonica var. discolor were closely related, with S. japonica var. timoriensis serving as their sister taxon. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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15 pages, 620 KiB

Open AccessEditor’s ChoiceArticle

Objective Assessments of Smoking and Drinking Outperform Clinical Phenotypes in Predicting Variance in Epigenetic Aging

by Robert Philibert, Man-Kit Lei, Mei Ling Ong and Steven R. H. Beach

Genes 2024, 15(7), 869; https://doi.org/10.3390/genes15070869 - 2 Jul 2024

Cited by 4 | Viewed by 1309

Abstract

The reliability of the associations of the acceleration of epigenetic aging (EA) indices with clinical phenotypes other than for smoking and drinking is poorly understood. Furthermore, the majority of clinical phenotyping studies have been conducted using data from subjects of European ancestry. In [...] Read more.

The reliability of the associations of the acceleration of epigenetic aging (EA) indices with clinical phenotypes other than for smoking and drinking is poorly understood. Furthermore, the majority of clinical phenotyping studies have been conducted using data from subjects of European ancestry. In order to address these limitations, we conducted clinical, physiologic, and epigenetic assessments of a cohort of 278 middle-aged African American adults and analyzed the associations with the recently described principal-components-trained version of GrimAge (i.e., PC-GrimAge) and with the DunedinPACE (PACE) index using regression analyses. We found that 74% of PC-GrimAge accelerated aging could be predicted by a simple baseline model consisting of age, sex, and methylation-sensitive digital PCR (MSdPCR) assessments of smoking and drinking. The addition of other serological, demographic, and medical history variables or PACE values did not meaningfully improve the prediction, although some variables did significantly improve the model fit. In contrast, clinical variables mapping to cardiometabolic syndrome did independently contribute to the prediction of PACE values beyond the baseline model. The PACE values were poorly correlated with the GrimAge values (r = 0.2), with little overlap in variance explained other than that conveyed by smoking and drinking. The results suggest that EA indices may differ in the clinical information that they provide and may have significant limitations as screening tools to guide patient care. Full article

(This article belongs to the Section Epigenomics)

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14 pages, 1960 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Analysis Identified Quantitative Trait Loci (QTLs) Underlying Drought-Related Traits in Cultivated Peanut (Arachis hypogaea L.)

by Phat Dang, Jinesh Patel, Ron Sorensen, Marshall Lamb and Charles Y. Chen

Genes 2024, 15(7), 868; https://doi.org/10.3390/genes15070868 - 2 Jul 2024

Cited by 2 | Viewed by 1490

Abstract

Drought is a destructive abiotic stress that affects all critical stages of peanut growth such as emergence, flowering, pegging, and pod filling. The development of a drought-tolerant variety is a sustainable strategy for long-term peanut production. The U.S. mini-core peanut germplasm collection was [...] Read more.

Drought is a destructive abiotic stress that affects all critical stages of peanut growth such as emergence, flowering, pegging, and pod filling. The development of a drought-tolerant variety is a sustainable strategy for long-term peanut production. The U.S. mini-core peanut germplasm collection was evaluated for drought tolerance to the middle-season drought treatment phenotyping for pod weight, pod count, relative water content (RWC), specific leaf area (SLA), leaf dry matter content (LDMC), and drought rating. A genome-wide association study (GWAS) was performed to identify minor and major QTLs. A total of 144 QTLs were identified, including 18 significant QTLs in proximity to 317 candidate genes. Ten significant QTLs on linkage groups (LGs) A03, A05, A06, A07, A08, B04, B05, B06, B09, and B10 were associated with pod weight and pod count. RWC stages 1 and 2 were correlated with pod weight, pod count, and drought rating. Six significant QTLs on LGs A04, A07, B03, and B04 were associated with RWC stages 1 and 2. Drought rating was negatively correlated with pod yield and pod count and was associated with a significant QTL on LG A06. Many QTLs identified in this research are novel for the evaluated traits, with verification that the pod weight shared a significant QTL on chromosome B06 identified in other research. Identified SNP markers and the associated candidate genes provide a resource for molecular marker development. Verification of candidate genes surrounding significant QTLs will facilitate the application of marker-assisted peanut breeding for drought tolerance. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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28 pages, 826 KiB

Open AccessEditor’s ChoiceReview

Congenital Heart Disease and Genetic Changes in Folate/Methionine Cycles

by Nataša Karas Kuželički and Bojan Doljak

Genes 2024, 15(7), 872; https://doi.org/10.3390/genes15070872 - 2 Jul 2024

Cited by 4 | Viewed by 2295

Abstract

Congenital heart disease is one of the most common congenital malformations and thus represents a considerable public health burden. Hence, the identification of individuals and families with an increased genetic predisposition to congenital heart disease (CHD) and its possible prevention is important. Even [...] Read more.

Congenital heart disease is one of the most common congenital malformations and thus represents a considerable public health burden. Hence, the identification of individuals and families with an increased genetic predisposition to congenital heart disease (CHD) and its possible prevention is important. Even though CHD is associated with the lack of folate during early pregnancy, the genetic background of folate and methionine metabolism perturbations and their influence on CHD risk is not clear. While some genes, such as those coding for cytosolic enzymes of folate/methionine cycles, have been extensively studied, genetic studies of folate transporters (de)glutamation enzymes and mitochondrial enzymes of the folate cycle are lacking. Among genes coding for cytoplasmic enzymes of the folate cycle, MTHFR, MTHFD1, MTR, and MTRR have the strongest association with CHD, while among genes for enzymes of the methionine cycle BHMT and BHMT2 are the most prominent. Among mitochondrial folate cycle enzymes, MTHFD2 plays the most important role in CHD formation, while FPGS was identified as important in the group of (de)glutamation enzymes. Among transporters, the strongest association with CHD was demonstrated for SLC19A1. Full article

(This article belongs to the Special Issue Genetics, Genomics and Precision Medicine in Heart Diseases)

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15 pages, 6926 KiB

Open AccessEditor’s ChoiceArticle

Identification and Expression Analysis of UPS Gene Family in Potato

by Wenyue Huang, Yifei Lu, Bi Ren, Fuchun Zeng, Yongjian Liu, Liming Lu and Liqin Li

Genes 2024, 15(7), 870; https://doi.org/10.3390/genes15070870 - 2 Jul 2024

Viewed by 1159

Abstract

Ureide permeases (UPSs) mediate the transport of ureides, including allantoin and allantoate, which act as nitrogen-transporting compounds in plants and have recently been found to play a role in cellular signaling. To date, UPSs have not been reported in potato, and their identification [...] Read more.

Ureide permeases (UPSs) mediate the transport of ureides, including allantoin and allantoate, which act as nitrogen-transporting compounds in plants and have recently been found to play a role in cellular signaling. To date, UPSs have not been reported in potato, and their identification is important for further function studies and for understanding molecular mechanisms of plant adverse responses. Based on potato genomic data, we identified 10 StUPS genes in potato (Solanum tuberosum L.). Then, we conducted a comprehensive study of the identified StUPS genes using bioinformatics methods. Genome phylogenetic and genomic localization analyses revealed that StUPSs can be classified into four categories, are highly homologous to Arabidopsis thaliana UPS members, and are distributed on three chromosomes. The six StUPS genes were investigated by RT–qPCR, and the findings indicated that all of these genes are involved in the response to several stresses, including low nitrogen, cold, ABA, salt, H₂O_2, and drought. This study establishes a strong theoretical framework for investigating the function of potato UPS genes, as well as the molecular mechanisms underlying the responses of these genes to various environmental stresses. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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18 pages, 2397 KiB

Open AccessEditor’s ChoiceArticle

Gene Expression Profiling and Qualitative Characteristics in Delaying Flesh Softening of Avocado Fruits

by Ourania Anagnostopoulou, Georgios Tsaniklidis, Konstantinos Paschalidis and Filippos Ververidis

Genes 2024, 15(7), 860; https://doi.org/10.3390/genes15070860 - 1 Jul 2024

Cited by 1 | Viewed by 1322

Abstract

In this research, qualitative characteristics were studied under different post-harvest treatments in Hass and Fuerte cultivars of avocado (Persea americana) fruits. The post-harvest treatments performed in fruits of these cultivars comprised Ethrel application and plastic film (membrane) covering. The measurements of [...] Read more.

In this research, qualitative characteristics were studied under different post-harvest treatments in Hass and Fuerte cultivars of avocado (Persea americana) fruits. The post-harvest treatments performed in fruits of these cultivars comprised Ethrel application and plastic film (membrane) covering. The measurements of qualitative characteristics were related to color; flesh consistency; measurements of titratable acidity, total soluble solids, percentage of total phenolic contents, and ascorbic peroxidase activity; and the real-time (quantitative) polymerase chain reaction (qPCR) of gene expression and enzyme activities of phenylalanine ammonia-lyase (PAL) and beta-galactosidase (β-gal). The experiments found that the application of plastic film has excellent results in retaining qualitative characteristics and enzyme activities via maintaining firmness in higher levels. The plastic film covering appeared to delay ripening without the use of chemicals and, therefore, it has the potential to extend the duration of the post-harvest life of the avocado fruit. Variations between the two cultivars were found in the measurements of total soluble solids (Fuerte cultivar showed an increase of 22%, whereas Hass cultivar showed an increase of 120% in Brix values) and total phenolic contents (Fuerte cultivar showed a decrease of 16% and Hass cultivar showed an increase of 29%). It is worth noting that PAL’s activity increased significantly (over 44%), as compared to other treatments, and β-galactosidase’s activity decreased, as compared to other treatments. In conclusion, plastic film covering results in a decrease in the activity of β-galactosidase, as shown by the reaction of hydrolysis (enzyme activity) but also from the expression of the related genes. Full article

(This article belongs to the Special Issue Advances in Genetics and Genomics of Plants)

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23 pages, 4160 KiB

Open AccessEditor’s ChoiceArticle

Intermolecular Gene Conversion for the Equalization of Genome Copies in the Polyploid Haloarchaeon Haloferax volcanii: Identification of Important Proteins

by Hanna Özer, Daniel Wasser, Lara Sandner and Jörg Soppa

Genes 2024, 15(7), 861; https://doi.org/10.3390/genes15070861 - 1 Jul 2024

Cited by 2 | Viewed by 1671

Abstract

The model haloarchaeon Haloferax volcanii is polyploid with about 20 copies of its major chromosome. Recently it has been described that highly efficient intermolecular gene conversion operates in H. volcanii to equalize the chromosomal copies. In the current study, 24 genes were selected [...] Read more.

The model haloarchaeon Haloferax volcanii is polyploid with about 20 copies of its major chromosome. Recently it has been described that highly efficient intermolecular gene conversion operates in H. volcanii to equalize the chromosomal copies. In the current study, 24 genes were selected that encode proteins with orthologs involved in gene conversion or homologous recombination in archaea, bacteria, or eukaryotes. Single gene deletion strains of 22 genes and a control gene were constructed in two parent strains for a gene conversion assay; only radA and radB were shown to be essential. Protoplast fusions were used to generate strains that were heterozygous for the gene HVO_2528, encoding an enzyme for carotinoid biosynthesis. It was revealed that a lack of six of the proteins did not influence the efficiency of gene conversion, while sixteen mutants had severe gene conversion defects. Notably, lack of paralogous proteins of gene families had very different effects, e.g., mutant Δrad25b had no phenotype, while mutants Δrad25a, Δrad25c, and Δrad25d were highly compromised. Generation of a quadruple rad25 and a triple sph deletion strain also indicated that the paralogs have different functions, in contrast to sph2 and sph4, which cannot be deleted simultaneously. There was no correlation between the severity of the phenotypes and the respective transcript levels under non-stressed conditions, indicating that gene expression has to be induced at the onset of gene conversion. Phylogenetic trees of the protein families Rad3/25, MutL/S, and Sph/SMC/Rad50 were generated to unravel the history of the paralogous proteins of H. volcanii. Taken together, unselected intermolecular gene conversion in H. volcanii involves at least 16 different proteins, the molecular roles of which can be studied in detail in future projects. Full article

(This article belongs to the Section Microbial Genetics and Genomics)

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17 pages, 2179 KiB

Open AccessEditor’s ChoiceArticle

A-to-I Editing Is Subtype-Specific in Non-Hodgkin Lymphomas

by Cai Chen and Ralf Bundschuh

Genes 2024, 15(7), 864; https://doi.org/10.3390/genes15070864 - 1 Jul 2024

Cited by 1 | Viewed by 1282

Abstract

Cancer is a complex and heterogeneous disease, in which a number of genetic and epigenetic changes occur in tumor onset and progression. Recent studies indicate that changes at the RNA level are also involved in tumorigenesis, such as adenosine-to-inosine (A-to-I) RNA editing. Here, [...] Read more.

Cancer is a complex and heterogeneous disease, in which a number of genetic and epigenetic changes occur in tumor onset and progression. Recent studies indicate that changes at the RNA level are also involved in tumorigenesis, such as adenosine-to-inosine (A-to-I) RNA editing. Here, we systematically investigate transcriptome-wide A-to-I editing events in a large number of samples from Non-Hodgkin lymphomas (NHLs). Using a computational pipeline that determines significant differences in editing level between NHL and normal samples at known A-to-I editing sites, we identify a number of differentially edited editing sites between NHL subtypes and normal samples. Most of the differentially edited sites are located in non-coding regions, and many such sites show a strong correlation between gene expression level and editing efficiency, indicating that RNA editing might have direct consequences for the cancer cell’s aberrant gene regulation status in these cases. Moreover, we establish a strong link between RNA editing and NHL by demonstrating that NHL and normal samples and even NHL subtypes can be distinguished based on genome-wide RNA editing profiles alone. Our study establishes a strong link between RNA editing, cancer and aberrant gene regulation in NHL. Full article

(This article belongs to the Section RNA)

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27 pages, 460 KiB

Open AccessEditor’s ChoiceReview

The CRISPR-Cas System and Clinical Applications of CRISPR-Based Gene Editing in Hematology with a Focus on Inherited Germline Predisposition to Hematologic Malignancies

by Rina Kansal

Genes 2024, 15(7), 863; https://doi.org/10.3390/genes15070863 - 1 Jul 2024

Cited by 3 | Viewed by 5641

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single-guide RNA (sgRNA)-based gene editing since the first report of repetitive sequences of unknown significance in [...] Read more.

Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single-guide RNA (sgRNA)-based gene editing since the first report of repetitive sequences of unknown significance in 1987 is fascinating, highly instructive, and inspiring for future advances in medicine. The recent approval of CRISPR-Cas9-based gene therapy to treat patients with severe sickle cell anemia and transfusion-dependent β-thalassemia has renewed hope for treating other hematologic diseases, including patients with a germline predisposition to hematologic malignancies, who would benefit greatly from the development of CRISPR-inspired gene therapies. The purpose of this paper is three-fold: first, a chronological description of the history of CRISPR-Cas9-sgRNA-based gene editing; second, a brief description of the current state of clinical research in hematologic diseases, including selected applications in treating hematologic diseases with CRISPR-based gene therapy, preceded by a brief description of the current tools being used in clinical genome editing; and third, a presentation of the current progress in gene therapies in inherited hematologic diseases and bone marrow failure syndromes, to hopefully stimulate efforts towards developing these therapies for patients with inherited bone marrow failure syndromes and other inherited conditions with a germline predisposition to hematologic malignancies. Full article

(This article belongs to the Special Issue Research Progress in Hematological Malignancies: A Molecular Genetics Perspective)

11 pages, 3049 KiB

Open AccessEditor’s ChoiceArticle

Expanding Genetic Counselor Roles: A Model for Global Research Development

by Colleen C. Muraresku, Elizabeth M. McCormick, Lydia Rockart, T. Blaine Crowley, Stephanie Asher, Amanda Back, Sarah M. Baldino, Emma Bedoukian, Allison D. Britt, Natalie Burrill, Cara Cacioppo, Dana Farengo Clark, Mary Egan Clark, Laura Conway, Laynie Dratch, Holly A. Dubbs, Nicole M. Engelhardt, Natalie Ginn, Christopher Gray, Tiff Hartman, Evan R. Hathaway, Katherine L. Helbig, Lily Hoffman-Andrews, Stefanie Kasperski, Beth A. Keena, Kierstin N. Keller, Jessica M. Long, Lauren Lulis, Laina Lusk, Daniel E. McGinn, Rebecca Mueller, Rache A. Paul, Lisa Pilchman, Jacquelyn Powers, Sarah E. Raible, Sara Reichert, Alyssa L. Rippert, Angela G. Arnold, Sarah M. Ruggiero, Erica Schindewolf, Katie Rose Sullivan, Shannon Terek, Bekah Wang, McKenzie Wells, Natalia Wisniewski, Renee Wright, Elisabeth McCarty Wood, Stacy Woyciechowski, Kristin Zelley, Kathleen D. Valverde and Donna M. McDonald-McGinn Show full author list Hide full author list

Genes 2024, 15(7), 867; https://doi.org/10.3390/genes15070867 - 1 Jul 2024

Viewed by 2389

Abstract

Purpose: Genetic counselors (GCs) increasingly play key roles in advancing genomic medicine through innovative research. Here, we examine one large cohort of GCs’ evolving contributions to the literature, with the goal of facilitating worldwide professional development for GCs through scholarly activities. Methods: Publications [...] Read more.

Purpose: Genetic counselors (GCs) increasingly play key roles in advancing genomic medicine through innovative research. Here, we examine one large cohort of GCs’ evolving contributions to the literature, with the goal of facilitating worldwide professional development for GCs through scholarly activities. Methods: Publications were cataloged by members of the Section of Genetic Counseling (Section), established at the Children’s Hospital of Philadelphia and the University of Pennsylvania in 2014, including publication year, journal, impact factor, and author position. Data were organized using the “My Bibliography” tool on the National Center for Biotechnology Information website and a Research Electronic Data Capture database created to initially collect manuscripts published through 30 June 2020. A subsequent survey captured publications through 5 February 2024. Results: An amount of 52 of 120 (43%) GCs shared their curriculum vitae/papers. 992 unique publications were identified from 1986 to 2024. Since 2013, no less than 32 papers were published annually by Section members and no less than 10 GCs contributed to publications yearly. Impact factors typically averaged >5.0 per year. Areas of foci diversified considerably since 2015. Conclusions: Here, we establish that GCs indeed contribute to scholarly work as evidenced by the number of publications alone. The establishment of an academic home may have contributed, given publications increased concurrent to launching the Section, providing a model for organizing GCs at institutions nationally and internationally. Highlighting such achievements will foster the expansion of GC roles in the era of precision genomic medicine and therapy. Considering ways to support GCs towards expanding these activities is equally important. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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22 pages, 2894 KiB

Open AccessEditor’s ChoiceArticle

Genotypic Identification of Trees Using DNA Barcodes and Microbiome Analysis of Rhizosphere Microbial Communities

by Liliana Hopkins, Kayla Yim, Ana Rumora, Melissa F. Baykus, Luisa Martinez and Luis Jimenez

Genes 2024, 15(7), 865; https://doi.org/10.3390/genes15070865 - 1 Jul 2024

Cited by 2 | Viewed by 1512

Abstract

DNA barcodes can provide accurate identification of plants. We used previously reported DNA primers targeting the internal transcribed spacer (ITS1) region of the nuclear ribosomal cistron, internal transcribed spacer (ITS2), and chloroplast trnL (UAA) intron to identify four trees at Bergen Community College. [...] Read more.

DNA barcodes can provide accurate identification of plants. We used previously reported DNA primers targeting the internal transcribed spacer (ITS1) region of the nuclear ribosomal cistron, internal transcribed spacer (ITS2), and chloroplast trnL (UAA) intron to identify four trees at Bergen Community College. Two of the four trees were identified as Acer rubrum and Fagus sylvatica. However, Quercus was only identified at the genus level, and the fourth tree did not show similar identification between barcodes. Next-generation sequencing of 16S rRNA genes showed that the predominant bacterial communities in the rhizosphere mainly consisted of the Pseudomonadota, Actinomycetota, Bacteroidota, and Acidobacteriota. A. rubrum showed the most diverse bacterial community while F. sylvatica was less diverse. The genus Rhodoplanes showed the highest relative bacterial abundance in all trees. Fungal ITS sequence analysis demonstrated that the communities predominantly consisted of the Ascomycota and Basidiomycota. Quercus showed the highest fungi diversity while F. sylvatica showed the lowest. Russula showed the highest abundance of fungi genera. Average similarity values in the rhizosphere for fungi communities at the phylum level were higher than for bacteria. However, at the genus level, bacterial communities showed higher similarities than fungi. Similarity values decreased at lower taxonomical levels for both bacteria and fungi, indicating each tree has selected for specific bacterial and fungal communities. This study confirmed the distinctiveness of the microbial communities in the rhizosphere of each tree and their importance in sustaining and supporting viability and growth but also demonstrating the limitations of DNA barcoding with the primers used in this study to identify genus and species for some of the trees. The optimization of DNA barcoding will require additional DNA sequences to enhance the resolution and identification of trees at the study site. Full article

(This article belongs to the Section Microbial Genetics and Genomics)

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13 pages, 4120 KiB

Open AccessEditor’s ChoiceArticle

Genetic Insights into the Historical Attribution of Variety Names of Sweet Chestnut (Castanea sativa Mill.) in Northern Italy

by Marta Cavallini, Gianluca Lombardo, Claudio Cantini, Mauro Gerosa and Giorgio Binelli

Genes 2024, 15(7), 866; https://doi.org/10.3390/genes15070866 - 1 Jul 2024

Viewed by 1530

Abstract

The sweet chestnut (Castanea sativa Mill.) is subject to the progressive disappearance of its traditional chestnut groves. In the northern part of Italy, where distribution of the sweet chestnut is fragmented, many local varieties continue to be identified mostly by oral tradition. [...] Read more.

The sweet chestnut (Castanea sativa Mill.) is subject to the progressive disappearance of its traditional chestnut groves. In the northern part of Italy, where distribution of the sweet chestnut is fragmented, many local varieties continue to be identified mostly by oral tradition. We characterised by SSRs eleven historically recognised varieties of sweet chestnut in the area surrounding Lake Como, with the goal of giving a genetic basis to the traditional classification. We performed classical analysis about differentiation and used Bayesian approaches to detect population structure and to reconstruct demography. The results revealed that historical and genetic classifications are loosely linked when chestnut fruits are just “castagne”, that is, normal fruits, but increasingly overlap where “marroni” (the most prized fruits) are concerned. Bayesian classification allowed us to identify a homogeneous gene cluster not recognised in the traditional assessment of the varieties and to reconstruct possible routes used for the propagation of sweet chestnut. We also reconstructed ancestral relationships between the different gene pools involved and dated ancestral lineages whose results fit with palynological data. We suggest that conservation strategies based on a genetic evaluation of the resource should also rely on traditional cultural heritage, which could reveal new sources of germplasm. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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8 pages, 548 KiB

Open AccessEditor’s ChoiceArticle

Lynch Syndrome and Thyroid Nodules: A Single Center Experience

by Irene Spinelli, Simona Moffa, Francesca Fianchi, Teresa Mezza, Francesca Cinti, Gianfranco Di Giuseppe, Clelia Marmo, Gianluca Ianiro, Francesca Romana Ponziani, Annalisa Tortora, Maria Elena Riccioni, Andrea Giaccari and Antonio Gasbarrini

Genes 2024, 15(7), 859; https://doi.org/10.3390/genes15070859 - 30 Jun 2024

Cited by 1 | Viewed by 1965

Abstract

Background: Lynch syndrome (LS) is a genetic disease with increased risk of colorectal cancer and other malignancies. There are few reported cases of thyroid cancer in LS patients. The aim of this study is to investigate the presence of thyroid nodules in LS [...] Read more.

Background: Lynch syndrome (LS) is a genetic disease with increased risk of colorectal cancer and other malignancies. There are few reported cases of thyroid cancer in LS patients. The aim of this study is to investigate the presence of thyroid nodules in LS patients and to explore their association with the genetic features of the disease. Methods: A retrospective and descriptive analysis was conducted to include all LS patients followed at the CEMAD (Centro Malattie Apparato Digerente) of Fondazione Policlinico Universitario A. Gemelli IRCCS. The characteristics of LS disease, gene mutations, and previous history of thyroid disease were evaluated. Majority of patients underwent thyroid ultrasound (US), and nodule cytology was performed when needed. Results: Of a total of 139 patients with LS, 110 patients were included in the study. A total of 103 patients (74%) underwent thyroid ultrasound examinations, and 7 patients (5%) had a previous history of thyroid disease (cancer or multinodular goiter). The mean age was 51.9 years. Thyroid nodules were found in 62 patients (60%) who underwent US, and 9 of them (14%) had suspicious features of malignancy, inducing a fine-needle aspiration biopsy. A cytologic analysis classified 7 of 9 cases (78%) as TIR2 and 2 (22%) as TIR3a. Between patients with nodular thyroid disease (single nodule, multinodular goiter, and cancer), most of them (25 patients, 36% of total) were carriers of the MSH6 mutation, while 22 (32%), 17 (24%), and 5 (7%) had MSH2, MLH1, and PMS2 mutations, respectively. Conclusions: A high prevalence of thyroid nodules was found in patients with LS, especially in MSH6-carrying patients. Performing at least one thyroid ultrasound examination is suggested for the detection of nodular thyroid disease in LS patients. Systematic investigations are needed to estimate their prevalence, features, and risk of malignant transformation. Full article

(This article belongs to the Section Genetic Diagnosis)

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11 pages, 733 KiB

Open AccessEditor’s ChoiceArticle

Variation of the 3’RR1 HS1.2 Enhancer and Its Genomic Context

by Carla Jodice, Patrizia Malaspina, Bianca Maria Ciminelli, Cristina Martinez-Labarga, Michela Biancolella, Giuseppe Novelli and Andrea Novelletto

Genes 2024, 15(7), 856; https://doi.org/10.3390/genes15070856 - 29 Jun 2024

Cited by 1 | Viewed by 1355

Abstract

In humans, the HS1.2 enhancer in the Ig heavy-chain locus is modular, with length polymorphism. Previous studies have shown the following features for this variation: (i) strong population structuring; (ii) association with autoimmune diseases; and (iii) association with developmental changes in Ig expression. [...] Read more.

In humans, the HS1.2 enhancer in the Ig heavy-chain locus is modular, with length polymorphism. Previous studies have shown the following features for this variation: (i) strong population structuring; (ii) association with autoimmune diseases; and (iii) association with developmental changes in Ig expression. The HS1.2 region could then be considered as a contributor to inter-individual diversity in humoral response in adaptive immunity. We experimentally determined the HS1.2-length class genotype in 72 of the 1000 Genomes CEU cell lines and assigned the HS1.2 alleles to haplotypes defined by 18 landmark SNPs. We also sequenced the variable portion and ~200 bp of the flanking DNA of 34 HS1.2 alleles. Furthermore, we computationally explored the ability of different allelic arrangements to bind transcription factors. Non-random association between HS1.2 and Gm allotypes in the European population clearly emerged. We show a wealth of variation in the modular composition of HS1.2, with five SNPs further contributing to diversity. Longer alleles offer more potential sites for binding but, for same-length alleles, SNP variation creates/destroys potential binding sites. Altogether, the arrangements of modules and SNP alleles both inside and outside HS1.2 denote an organization of diversity far from randomness. In the context of the strong divergence of human populations for this genomic region and the reported disease associations, our results suggest that selective forces shaped the pattern of its diversity. Full article

(This article belongs to the Special Issue Evolution of Non-coding Elements in Genome Biology)

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24 pages, 2502 KiB

Open AccessEditor’s ChoicePerspective

Integrated Approaches and Practical Recommendations in Patient Care Identified with 5q Spinal Muscular Atrophy through Newborn Screening

by Vanessa L. Romanelli Tavares, Rodrigo Holanda Mendonça, Maytê S. Toledo, Sônia M. Hadachi, Carmela M. Grindler, Edmar Zanoteli, Wilson Marques, Jr., Acary S. B. Oliveira, Paulo Breinis, Maria da P. A. Morita and Marcondes C. França, Jr.

Genes 2024, 15(7), 858; https://doi.org/10.3390/genes15070858 - 29 Jun 2024

Cited by 1 | Viewed by 2195

Abstract

In recent years, significant progress has been made in 5q Spinal Muscular Atrophy therapeutics, emphasizing the importance of early diagnosis and intervention for better clinical outcomes. Characterized by spinal cord motor neuron degeneration, 5q-SMA leads to muscle weakness, swallowing difficulties, respiratory insufficiency, and [...] Read more.

In recent years, significant progress has been made in 5q Spinal Muscular Atrophy therapeutics, emphasizing the importance of early diagnosis and intervention for better clinical outcomes. Characterized by spinal cord motor neuron degeneration, 5q-SMA leads to muscle weakness, swallowing difficulties, respiratory insufficiency, and skeletal deformities. Recognizing the pre-symptomatic phases supported by screening and confirmatory genetic tests is crucial for early diagnosis. This work addresses key considerations in implementing 5q-SMA screening within the Brazilian National Newborn Screening Program and explores Brazil’s unique challenges and opportunities, including genetic tests, time-to-patient referral to specialized centers, program follow-up, and treatment algorithms. We aim to guide healthcare professionals and policymakers, facilitating global discussions, including Latin American countries, and knowledge-sharing on this critical subject to improve the care for newborns identified with 5q SMA. Full article

(This article belongs to the Special Issue Genetic Newborn Screening)

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19 pages, 2854 KiB

Open AccessEditor’s ChoiceArticle

New Observations of the Effects of the Cytoplasm of Aegilops kotschyi Boiss. in Bread Wheat Triticum aestivum L.

by Chaolan Fan, Joanna Melonek and Adam J. Lukaszewski

Genes 2024, 15(7), 855; https://doi.org/10.3390/genes15070855 - 28 Jun 2024

Cited by 1 | Viewed by 1607

Abstract

The cytoplasm of Aegilops kotschyi is known for the induction of male sterility and haploidy in wheat. Both systems originally appeared rather simple, but manipulation of the standard chromosome constitution of the nuclear genome revealed additional interactions. This study shows that while there [...] Read more.

The cytoplasm of Aegilops kotschyi is known for the induction of male sterility and haploidy in wheat. Both systems originally appeared rather simple, but manipulation of the standard chromosome constitution of the nuclear genome revealed additional interactions. This study shows that while there is little or no allelic variation at the main fertility restorer locus Rf^multi on chromosome arm 1BS, additional genes may also be involved in the nuclear–mitochondrial genome interactions, affecting not only male fertility but also the growth rate, from pollen competition for fertilization and early endosperm divisions all the way to seed size and plant maturity. Some of these effects appear to be of a sporophytic nature; others are gametophytic. Induction of parthenogenesis by a rye inducer in conjunction with the Ae. kotschyi cytoplasm is well known. However, here we show that the cytoplasmic-nuclear interactions affect all aspects of double fertilization: producing maternal haploids from unfertilized eggs, diploids from fertilized eggs or synergids, embryo-less kernels, and fertilized eggs without fertilization of the double nucleus in the embryo sack. It is unclear how frequent the inducers of parthenogenesis are, as variation, if any, is obscured by suppressors present in the wheat genome. Genetic dissection of a single wheat accession revealed five distinct loci affecting the rate of maternal haploid production: four acting as suppressors and one as an enhancer. Only when the suppressing haplotypes are confirmed may it be possible to the identify genetic variation of haploidy inducers, map their position(s), and determine their nature and the mode of action. Full article

(This article belongs to the Special Issue Genetics and Breeding of Polyploid Plants)

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12 pages, 5286 KiB

Open AccessEditor’s ChoiceArticle

Potential Involvement of MnCYP710A11 in Botrytis cinerea Resistance in Arabidopsis thaliana and Morus notabilis

by Hui An, Donghao Wang, Lin Yu, Hongshun Wu, Yue Qin, Shihao Zhang, Xianling Ji, Youchao Xin and Xiaodong Li

Genes 2024, 15(7), 853; https://doi.org/10.3390/genes15070853 - 28 Jun 2024

Viewed by 1172

Abstract

Cytochrome P450 (CYP) is a crucial oxidoreductase enzyme that plays a significant role in plant defense mechanisms. In this study, a specific cytochrome P450 gene (MnCYP710A11) was discovered in mulberry (Morus notabilis). Bioinformatic analysis and expression pattern analysis were [...] Read more.

Cytochrome P450 (CYP) is a crucial oxidoreductase enzyme that plays a significant role in plant defense mechanisms. In this study, a specific cytochrome P450 gene (MnCYP710A11) was discovered in mulberry (Morus notabilis). Bioinformatic analysis and expression pattern analysis were conducted to elucidate the involvement of MnCYP710A11 in combating Botrytis cinerea infection. After the infection of B. cinerea, there was a notable increase in the expression of MnCYP710A11. MnCYP710A11 is overexpressed in Arabidopsis and mulberry and strongly reacts to B. cinerea. The overexpression of the MnCYP710A11 gene in Arabidopsis and mulberry led to a substantial enhancement in resistance against B. cinerea, elevated catalase (CAT) activity, increased proline content, and reduced malondialdehyde (MDA) levels. At the same time, H₂O₂ and O₂⁻ levels in MnCYP710A11 transgenic Arabidopsis were decreased, which reduced the damage of ROS accumulation to plants. Furthermore, our research indicates the potential involvement of MnCYP710A11 in B. cinerea resistance through the modulation of other resistance-related genes. These findings establish a crucial foundation for gaining deeper insights into the role of cytochrome P450 in mulberry plants. Full article

(This article belongs to the Collection Feature Papers: 'Plant Genetics and Genomics' Section)

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10 pages, 4163 KiB

Open AccessEditor’s ChoiceCase Report

EDA Missense Variant in a Cat with X-Linked Hypohidrotic Ectodermal Dysplasia

by Stefan J. Rietmann, Noëlle Cochet-Faivre, Helene Dropsy, Vidhya Jagannathan, Lucie Chevallier and Tosso Leeb

Genes 2024, 15(7), 854; https://doi.org/10.3390/genes15070854 - 28 Jun 2024

Viewed by 1921

Abstract

Hypohidrotic ectodermal dysplasia is a developmental defect characterized by sparse or absent hair, missing or malformed teeth and defects in eccrine glands. Loss-of-function variants in the X-chromosomal EDA gene have been reported to cause hypohidrotic ectodermal dysplasia in humans, mice, dogs and cattle. [...] Read more.

Hypohidrotic ectodermal dysplasia is a developmental defect characterized by sparse or absent hair, missing or malformed teeth and defects in eccrine glands. Loss-of-function variants in the X-chromosomal EDA gene have been reported to cause hypohidrotic ectodermal dysplasia in humans, mice, dogs and cattle. We investigated a male cat exhibiting diffuse truncal alopecia with a completely absent undercoat. The cat lacked several teeth, and the remaining teeth had an abnormal conical shape. Whole-genome sequencing revealed a hemizygous missense variant in the EDA gene, XM_011291781.3:c.1042G>A or XP_011290083.1:p.(Ala348Thr). The predicted amino acid exchange is located in the C-terminal TNF signaling domain of the encoded ectodysplasin. The corresponding missense variant in the human EDA gene, p.Ala349Thr, has been reported as a recurring pathogenic variant in several human patients with X-linked hypohidrotic ectodermal dysplasia. The identified feline variant therefore represents the likely cause of the hypohidrotic ectodermal dysplasia in the investigated cat, and the genetic investigation confirmed the suspected clinical diagnosis. This is the first report of an EDA-related hypohidrotic ectodermal dysplasia in cats. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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15 pages, 1980 KiB

Open AccessEditor’s ChoiceArticle

Deafness DFNB128 Associated with a Recessive Variant of Human MAP3K1 Recapitulates Hearing Loss of Map3k1-Deficient Mice

by Rabia Faridi, Rizwan Yousaf, Sayaka Inagaki, Rafal Olszewski, Shoujun Gu, Robert J. Morell, Elizabeth Wilson, Ying Xia, Tanveer Ahmed Qaiser, Muhammad Rashid, Cristina Fenollar-Ferrer, Michael Hoa, Sheikh Riazuddin and Thomas B. Friedman

Genes 2024, 15(7), 845; https://doi.org/10.3390/genes15070845 - 27 Jun 2024

Viewed by 1748

Abstract

Deafness in vertebrates is associated with variants of hundreds of genes. Yet, many mutant genes causing rare forms of deafness remain to be discovered. A consanguineous Pakistani family segregating nonsyndromic deafness in two sibships were studied using microarrays and exome sequencing. A 1.2 [...] Read more.

Deafness in vertebrates is associated with variants of hundreds of genes. Yet, many mutant genes causing rare forms of deafness remain to be discovered. A consanguineous Pakistani family segregating nonsyndromic deafness in two sibships were studied using microarrays and exome sequencing. A 1.2 Mb locus (DFNB128) on chromosome 5q11.2 encompassing six genes was identified. In one of the two sibships of this family, a novel homozygous recessive variant NM_005921.2:c.4460G>A p.(Arg1487His) in the kinase domain of MAP3K1 co-segregated with nonsyndromic deafness. There are two previously reported Map3k1-kinase-deficient mouse models that are associated with recessively inherited syndromic deafness. MAP3K1 phosphorylates serine and threonine and functions in a signaling pathway where pathogenic variants of HGF, MET, and GAB1 were previously reported to be associated with human deafness DFNB39, DFNB97, and DFNB26, respectively. Our single-cell transcriptome data of mouse cochlea mRNA show expression of Map3k1 and its signaling partners in several inner ear cell types suggesting a requirement of wild-type MAP3K1 for normal hearing. In contrast to dominant variants of MAP3K1 associated with Disorders of Sex Development 46,XY sex-reversal, our computational modeling of the recessive substitution p.(Arg1487His) predicts a subtle structural alteration in MAP3K1, consistent with the limited phenotype of nonsyndromic deafness. Full article

(This article belongs to the Special Issue Molecular Basis of Rare Genetic Diseases)

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16 pages, 304 KiB

Open AccessEditor’s ChoiceArticle

Genetic Markers Related to Meat Quality Properties in Fattened HF and HF x Charolaise Steers

by Piotr Kostusiak, Emilia Bagnicka, Beata Żelazowska, Magdalena Zalewska, Tomasz Sakowski, Jan Slósarz, Marcin Gołębiewski and Kamila Puppel

Genes 2024, 15(7), 843; https://doi.org/10.3390/genes15070843 - 27 Jun 2024

Cited by 1 | Viewed by 2307

Abstract

This study involved 45 Holstein and 60 Holstein-Charolaise steers, tailored with specific diets according to breed and rearing systems. DNA genotyping was conducted for DGAT1, LEP, SCD1, SREBF1, and TG genes to investigate their impact on carcass conformation traits, beef quality traits, and [...] Read more.

This study involved 45 Holstein and 60 Holstein-Charolaise steers, tailored with specific diets according to breed and rearing systems. DNA genotyping was conducted for DGAT1, LEP, SCD1, SREBF1, and TG genes to investigate their impact on carcass conformation traits, beef quality traits, and sensory quality traits. The results showed associations between the genetic variants and the analyzed traits. Specifically, DGAT1 was found to affect drip loss, meat brightness, and color saturation. The TG gene was associated with marbling and meat color. LEP influenced trim fat and pH levels, while SCD1 was linked to metabolic energy live weight gains, and pH levels. SREBF1 was related to fatness. Full article

(This article belongs to the Section Animal Genetics and Genomics)

13 pages, 2998 KiB

Open AccessEditor’s ChoiceArticle

Identification and Spatiotemporal Expression of a Putative New GABA Receptor Subunit in the Human Body Louse Pediculus humanus humanus

by Omar Hashim, Berthine Toubaté, Claude L. Charvet, Aimun A. E. Ahmed, Cédric Neveu, Isabelle Dimier-Poisson, Françoise Debierre-Grockiego and Catherine Dupuy

Genes 2024, 15(7), 844; https://doi.org/10.3390/genes15070844 - 27 Jun 2024

Viewed by 1209

Abstract

The human louse (Pediculus humanus) is an obligatory blood feeding ectoparasite with two ecotypes: the human body louse (Pediculus humanus humanus), a competent vector of several bacterial pathogens, and the human head louse (Pediculus humanus capitis), responsible [...] Read more.

The human louse (Pediculus humanus) is an obligatory blood feeding ectoparasite with two ecotypes: the human body louse (Pediculus humanus humanus), a competent vector of several bacterial pathogens, and the human head louse (Pediculus humanus capitis), responsible for pediculosis and affecting millions of people around the globe. GABA (γ-aminobutyric acid) receptors, members of the cys-loop ligand gated ion channel superfamily, are among the main pharmacological targets for insecticides. In insects, there are four subunits of GABA receptors: resistant-to-dieldrin (RDL), glycin-like receptor of drosophila (GRD), ligand-gated chloride channel homologue3 (LCCH3), and 8916 are well described and form distinct phylogenetic clades revealing orthologous relationships. Our previous studies in the human body louse confirmed that subunits Phh-RDL, Phh-GRD, and Phh-LCCH3 are well clustered in their corresponding clades. In the present work, we cloned and characterized a putative new GABA receptor subunit in the human body louse that we named HoCas, for Homologous to Cys-loop α like subunit. Extending our analysis to arthropods, HoCas was found to be conserved and clustered in a new (fifth) phylogenetic clade. Interestingly, the gene encoding this subunit is ancestral and has been lost in some insect orders. Compared to the other studied GABA receptor subunits, HoCas exhibited a relatively higher expression level in all development stages and in different tissues of human body louse. These findings improved our understanding of the complex nature of GABA receptors in Pediculus humanus and more generally in arthropods. Full article

(This article belongs to the Special Issue Advances in Molecular Microbiology and Parasitology)

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14 pages, 821 KiB

Open AccessEditor’s ChoiceArticle

Structural Differences between the Genomes of Deinococcus radiodurans Strains from Different Laboratories

by Ksenija Zahradka, Davor Zahradka and Jelena Repar

Genes 2024, 15(7), 847; https://doi.org/10.3390/genes15070847 - 27 Jun 2024

Viewed by 1709

Abstract

The bacterium Deinococcus radiodurans is known to efficiently and accurately reassemble its genome after hundreds of DNA double-strand breaks (DSBs). Only at very large amounts of radiation-induced DSBs is this accuracy affected in the wild-type D. radiodurans, causing rearrangements in its genome [...] Read more.

The bacterium Deinococcus radiodurans is known to efficiently and accurately reassemble its genome after hundreds of DNA double-strand breaks (DSBs). Only at very large amounts of radiation-induced DSBs is this accuracy affected in the wild-type D. radiodurans, causing rearrangements in its genome structure. However, changes in its genome structure may also be possible during the propagation and storage of cell cultures. We investigate this possibility by listing structural differences between three completely sequenced genomes of D. radiodurans strains with a recent common ancestor—the type strain stored and sequenced in two different laboratories (of the ATCC 13939 lineage) and the first sequenced strain historically used as the reference (ATCC BAA-816). We detected a number of structural differences and found the most likely mechanisms behind them: (i) transposition/copy number change in mobile interspersed repeats—insertion sequences and small non-coding repeats, (ii) variable number of monomers within tandem repeats, (iii) deletions between long direct DNA repeats, and (iv) deletions between short (4–10 bp) direct DNA repeats. The most surprising finding was the deletions between short repeats because it indicates the utilization of a less accurate DSB repair mechanism in conditions in which a more accurate one should be both available and preferred. The detected structural differences, as well as SNPs and short indels, while being important footprints of deinococcal DNA metabolism and repair, are also a valuable resource for researchers using these D. radiodurans strains. Full article

(This article belongs to the Section Microbial Genetics and Genomics)

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14 pages, 1740 KiB

Open AccessEditor’s ChoiceArticle

Genomic Regions Associated with Resistance to Gastrointestinal Parasites in Australian Merino Sheep

by Brenda Vera, Elly A. Navajas, Pablo Peraza, Beatriz Carracelas, Elize Van Lier and Gabriel Ciappesoni

Genes 2024, 15(7), 846; https://doi.org/10.3390/genes15070846 - 27 Jun 2024

Cited by 2 | Viewed by 2041

Abstract

The objective of this study was to identify genomic regions and genes associated with resistance to gastrointestinal nematodes in Australian Merino sheep in Uruguay, using the single-step GWAS methodology (ssGWAS), which is based on genomic estimated breeding values (GEBVs) obtained from a combination [...] Read more.

The objective of this study was to identify genomic regions and genes associated with resistance to gastrointestinal nematodes in Australian Merino sheep in Uruguay, using the single-step GWAS methodology (ssGWAS), which is based on genomic estimated breeding values (GEBVs) obtained from a combination of pedigree, genomic, and phenotypic data. This methodology converts GEBVs into SNP effects. The analysis included 26,638 animals with fecal egg count (FEC) records obtained in two independent parasitic cycles (FEC1 and FEC2) and 1700 50K SNP genotypes. The comparison of genomic regions was based on genetic variances (gVar(%)) explained by non-overlapping regions of 20 SNPs. For FEC1 and FEC2, 18 and 22 genomic windows exceeded the significance threshold (gVar(%) ≥ 0.22%), respectively. The genomic regions with strong associations with FEC1 were located on chromosomes OAR 2, 6, 11, 21, and 25, and for FEC2 on OAR 5, 6, and 11. The proportion of genetic variance attributed to the top windows was 0.83% and 1.9% for FEC1 and FEC2, respectively. The 33 candidate genes shared between the two traits were subjected to enrichment analysis, revealing a marked enrichment in biological processes related to immune system functions. These results contribute to the understanding of the genetics underlying gastrointestinal parasite resistance and its implications for other productive and welfare traits in animal breeding programs. Full article

(This article belongs to the Special Issue Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding)

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9 pages, 239 KiB

Open AccessEditor’s ChoiceArticle

by Raffaele Falsaperla, Vincenzo Sortino, Marina Antonietta Schinocca, Gaia Fusto, Roberta Rizzo, Chiara Barberi, Martino Ruggieri and Xena Giada Pappalardo

Genes 2024, 15(7), 848; https://doi.org/10.3390/genes15070848 - 27 Jun 2024

Cited by 3 | Viewed by 1853

Abstract

PURA syndrome is a congenital developmental disorder caused by de novo mutations in the PURA gene, which encodes a DNA/RNA-binding protein essential for transcriptional and translational regulation. We present the case of an 11-year-old patient with a de novo frameshift variant in the [...] Read more.

PURA syndrome is a congenital developmental disorder caused by de novo mutations in the PURA gene, which encodes a DNA/RNA-binding protein essential for transcriptional and translational regulation. We present the case of an 11-year-old patient with a de novo frameshift variant in the PURA gene, identified through whole exome sequencing (WES). In addition to the classical PURA deficiency phenotype, our patient exhibited pronounced sialorrhea and seizures, which were effectively treated with the ketogenic diet (KD). Our integrative approach, combining a literature review and bioinformatics data, has led to the first documented clinical case showing improvement in both sialorrhea and seizures with KD treatment, a phenomenon not previously reported. Although a direct relationship between the de novo PURA mutation and the KD was not established, we identified a novel frameshift deletion associated with a new clinical phenotype. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

13 pages, 2025 KiB

Open AccessEditor’s ChoiceArticle

Swine Influenza Viruses Isolated from 2019 to 2022 in Shandong Province, China, Exemplify the Dominant Genotype

by Yuzhong Zhao, Lebin Han, Haotian Sang, Sidang Liu, Pingping Yang, Yanmeng Hou and Yihong Xiao

Genes 2024, 15(7), 849; https://doi.org/10.3390/genes15070849 - 27 Jun 2024

Cited by 1 | Viewed by 1469

Abstract

Swine influenza viruses (SIVs) have been circulating in swine globally and are potential threats to human health. During the surveillance of SIVs in Shandong Province, China, from 2019 to 2022, 21 reassortant G4 genotype Eurasian avian-like (EA) H1N1 subtypes containing genes from the [...] Read more.

Swine influenza viruses (SIVs) have been circulating in swine globally and are potential threats to human health. During the surveillance of SIVs in Shandong Province, China, from 2019 to 2022, 21 reassortant G4 genotype Eurasian avian-like (EA) H1N1 subtypes containing genes from the EA H1N1 (HA and NA), 2009 pandemic (pdm/09) H1N1 virus (PB2, PB1, PA, NP, and M), and classical swine (CS) H1N1 (NS) lineages were isolated. The analysis of the key functional amino acid sites in the isolated viruses showed that two mutation sites (190D and 225E) that preferentially bind to the human α2-6 sialic acid receptor were found in HA. In PB2, three mutation sites (271A, 590S, and 591R) that may increase mammalian fitness and a mutation site (431M) that increases pathogenicity in mice were found. A typical human signature marker that may promote infection in humans, 357K, was found in NP. The viruses could replicate efficiently in mouse lungs and turbinates, and one of the H1N1 isolates could replicate in mouse kidneys and brains without prior adaption, which indicates that the viruses potentially pose a threat to human health. Histopathological results showed that the isolated viruses caused typical bronchopneumonia and encephalitis in mice. The results indicate that G4 genotype H1N1 has potential transmissibility to humans, and surveillance should be enhanced, which could provide important information for assessing the pandemic potential of the viruses. Full article

(This article belongs to the Special Issue The Diversity and Evolution of the Animal Virome)

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19 pages, 10025 KiB

Open AccessEditor’s ChoiceArticle

Studies on Human Cultured Fibroblasts and Cutaneous Squamous Cell Carcinomas Suggest That Overexpression of Histone Variant H2A.J Promotes Radioresistance and Oncogenic Transformation

by Benjamin M. Freyter, Mutaz A. Abd Al-razaq, Markus Hecht, Christian Rübe and Claudia E. Rübe

Genes 2024, 15(7), 851; https://doi.org/10.3390/genes15070851 - 27 Jun 2024

Viewed by 1498

Abstract

Background: Cellular senescence in response to ionizing radiation (IR) limits the replication of damaged cells by causing permanent cell cycle arrest. However, IR can induce pro-survival signaling pathways that reduce the extent of radiation-induced cytotoxicity and promote the development of radioresistance. The differential [...] Read more.

Background: Cellular senescence in response to ionizing radiation (IR) limits the replication of damaged cells by causing permanent cell cycle arrest. However, IR can induce pro-survival signaling pathways that reduce the extent of radiation-induced cytotoxicity and promote the development of radioresistance. The differential incorporation of histone variant H2A.J has profound effects on higher-order chromatin organization and on establishing the epigenetic state of radiation-induced senescence. However, the precise epigenetic mechanism and function of H2A.J overexpression in response to IR exposure still needs to be elucidated. Methods: Primary (no target, NT) and genetically modified fibroblasts overexpressing H2A.J (H2A.J-OE) were exposed to 20 Gy and analyzed 2 weeks post-IR for radiation-induced senescence by immunohistochemistry and immunofluorescence microscopy. Transcriptome signatures were analyzed in (non-)irradiated NT and H2A.J-OE fibroblasts by RNA sequencing. Since H2A.J plays an important role in the epidermal homeostasis of human skin, the oncogenic potential of H2A.J was investigated in cutaneous squamous cell carcinoma (cSCC). The tissue microarrays of cSCC were analyzed for H2A.J protein expression pattern by automated image analysis. Results: In response to radiation-induced DNA damage, the overexpression of H2A.J impairs the formation of senescence-associated heterochromatin foci (SAHF), thereby inhibiting the SAHF-mediated silencing of proliferation-promoting genes. The dysregulated activation of cyclins and cyclin-dependent kinases disturbs cell cycle arrest in irradiated H2A.J-OE fibroblasts, thereby overcoming radiation-induced senescence. Comparative transcriptome analysis revealed significantly increased WNT16 signaling in H2A.J OE fibroblasts after IR exposure, promoting the fundamental mechanisms of tumor development and progression, including the activation of the epithelial–mesenchymal transition. The quantitative analysis of cSCCs revealed that undifferentiated tumors are associated with high nuclear H2A.J expression, related with greater oncogenic potential. Conclusion: H2A.J overexpression induces radioresistance and promotes oncogenic transformation through the activation of WNT16 signaling pathway functions. H2A.J-associated signatures may improve risk stratification by identifying patients with more aggressive cSCC who may require radiotherapy with increased doses. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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10 pages, 466 KiB

Open AccessEditor’s ChoiceArticle

Association of LPP and ZMIZ1 Gene Polymorphism with Celiac Disease in Subjects from Punjab, Pakistan

by Sumaira Zulfiqar, Amna Fiaz, Waqas Ahmed Khan, Misbah Hussain, Ansar Ali, Nadeem Ahmed, Basharat Ali and Muhammad Adnan Masood

Genes 2024, 15(7), 852; https://doi.org/10.3390/genes15070852 - 27 Jun 2024

Cited by 2 | Viewed by 1598

Abstract

Celiac disease (CD) is a complicated autoimmune disease that is caused by gluten sensitivity. It was commonly believed that CD only affected white Europeans, but recent findings show that it is also prevailing in some other racial groups, like South Asians, Caucasians, Africans, [...] Read more.

Celiac disease (CD) is a complicated autoimmune disease that is caused by gluten sensitivity. It was commonly believed that CD only affected white Europeans, but recent findings show that it is also prevailing in some other racial groups, like South Asians, Caucasians, Africans, and Arabs. Genetics plays a profound role in increasing the risk of developing CD. Genetic Variations in non-HLA genes such as LPP, ZMIZ1, CCR3, and many more influence the risk of CD in various populations. This study aimed to explore the association between LPP rs1464510 and ZMIZ1 rs1250552 and CD in the Punjabi Pakistani population. For this, a total of 70 human subjects were selected and divided into healthy controls and patients. Genotyping was performed using an in-house-developed tetra-amplification refractory mutation system polymerase chain reaction. Statistical analysis revealed a significant association between LPP rs1464510 (χ² = 4.421, p = 0.035) and ZMIZ1 rs1250552 (χ2 = 3.867, p = 0.049) and CD. Multinomial regression analysis showed that LPP rs1464510 A allele reduces the risk of CD by ~52% (OR 0.48, CI: 0.24–0.96, 0.037), while C allele-carrying subjects are at ~2.6 fold increased risk of CD (OR 3.65, CI: 1.25–10.63, 0.017). Similarly, the ZMIZ1 rs1250552 AG genotype significantly reduces the risk of CD by 73% (OR 0.26, CI: 0.077–0.867, p = 0.028). In summary, Genetic Variations in the LPP and ZMIZ1 genes influence the risk of CD in Punjabi Pakistani subjects. LPP rs1464510 A allele and ZMIZ1 AG genotype play a protective role and reduce the risk of CD. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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13 pages, 3785 KiB

Open AccessEditor’s ChoiceArticle

Sinuous Is a Claudin Required for Locust Molt in Locusta migratoria

by Yichao Zhang, Hongjing Li, Qiuyan Lan, Xiaoman Liu, Haihua Wu, Jianzhen Zhang, Xiaoming Zhao and Yanli Wang

Genes 2024, 15(7), 850; https://doi.org/10.3390/genes15070850 - 27 Jun 2024

Viewed by 992

Abstract

The epidermal cells of insects are polarized epithelial cells that play a pivotal role in the insect’s molting process. Sinuous, a pivotal structural protein involved in the formation of septate junctions among epithelial cells, is essential for its physiological function. In this study, [...] Read more.

The epidermal cells of insects are polarized epithelial cells that play a pivotal role in the insect’s molting process. Sinuous, a pivotal structural protein involved in the formation of septate junctions among epithelial cells, is essential for its physiological function. In this study, to determine whether sinuous participates in the regulation of insect molting, we identified the sinuous gene, Lmsinu, in Locusta migratoria, which encodes a protein belonging to the claudin family and shares 62.6% identity with Drosophila’s sinuous protein. Lmsinu is expressed in multiple tissues, and its expression level in the integument significantly increases prior to molting. Knockdown of Lmsinu in L. migratoria results in larval mortality during molting. Furthermore, hematoxylin and eosin and chitin staining demonstrate that the downregulation of Lmsinu led to a prolonged degradation process of the old cuticle during the molting process. Electron microscopy analysis further revealed that knockdown of Lmsinu disrupts the formation of septate junctions among epidermal cells, which are a monolayer of polarized epithelial cells, which may hinder the functionality of epidermal cells during the process of molting. In summary, these findings suggest that Lmsinu plays a role in nymph molting by regulating the formation of septate junctions among epidermal cells. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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8 pages, 224 KiB

Open AccessEditor’s ChoiceArticle

Newborn Screening for X-Linked Adrenoleukodystrophy (X-ALD): Biochemical, Molecular, and Clinical Characteristics of Other Genetic Conditions

by Carlos F. Mares Beltran, Christina G. Tise, Rebekah Barrick, Annie D. Niehaus, Rebecca Sponberg, Richard Chang, Gregory M. Enns and Jose E. Abdenur

Genes 2024, 15(7), 838; https://doi.org/10.3390/genes15070838 - 26 Jun 2024

Viewed by 2138

Abstract

The state of California (CA) added X-linked adrenoleukodystrophy (X-ALD) to newborn screening (NBS) in 2016 via the measurement of C26:0-lysophosphatidylcholine (C26:0-LPC) in a two-tier fashion, followed by sequencing of the ABCD1 gene. This has resulted in the identification of individuals with genetic conditions [...] Read more.

The state of California (CA) added X-linked adrenoleukodystrophy (X-ALD) to newborn screening (NBS) in 2016 via the measurement of C26:0-lysophosphatidylcholine (C26:0-LPC) in a two-tier fashion, followed by sequencing of the ABCD1 gene. This has resulted in the identification of individuals with genetic conditions beyond X-ALD that can also result in elevated C26:0-LPC by NBS. We describe the biochemical, molecular, and clinical characteristics of nine patients from two metabolic centers in California who screened positive by NBS for elevated C26:0-LPC between 2016 and 2022 and were ultimately diagnosed with a genetic condition other than X-ALD. Seven individuals were diagnosed with Zellweger spectrum disorder (ZSD) due to biallelic variants in PEX genes. One male was diagnosed with Klinefelter syndrome and one female was found to have an X chromosome contiguous gene deletion syndrome after the identification of a heterozygous VUS and hemizygous VUS variant in ABCD1, respectively. Patients with ZSD had significantly higher first- and second-tier C26:0-LPC levels compared to the two non-ZSD cases. Identification of children with ZSD and atypical patterns of ABCD1 variants is a secondary benefit of NBS for X-ALD, leading to earlier diagnosis, prompt therapeutic initiation, and more accurate genetic counseling. As screening for X-ALD continues via the measurement of C26:0-LPC, our knowledge of additional genetic conditions associated with elevated C26:0-LPC will continue to advance, allowing for increased recognition of other genetic disorders for which early intervention is warranted. Full article

(This article belongs to the Special Issue Genetic Newborn Screening)

11 pages, 4115 KiB

Open AccessEditor’s ChoiceArticle

ROS-Induced Autophagy of Skeletal Muscle Confers Resistance of Rice Flower Carp (Cyprinus carpio) to Short-Term Fasting

by Jia Cheng, Junhan Luo, Ziyang Xu, Zhouying Liu, Lingsheng Bao and Liangyi Xue

Genes 2024, 15(7), 840; https://doi.org/10.3390/genes15070840 - 26 Jun 2024

Cited by 2 | Viewed by 1800

Abstract

Starvation is one of the main stresses for fish due to food shortage, the evasion of predators, and intraspecific competition. This research evaluated the impact of brief fasting periods on reactive oxygen species (ROS) levels, antioxidant response, mRNA expression of antioxidants, autophagy-related signaling [...] Read more.

Starvation is one of the main stresses for fish due to food shortage, the evasion of predators, and intraspecific competition. This research evaluated the impact of brief fasting periods on reactive oxygen species (ROS) levels, antioxidant response, mRNA expression of antioxidants, autophagy-related signaling genes, and autophagosome development in the muscle tissue of rice flower carp. Following a three-day fasting period, the levels of ROS and MDA rose. Additionally, after 3 d of fasting, there was a notable upregulation of NRF2 and significant increases in the levels of GSH and the activities of enzymes such as SOD, CAT, GST, GR, and GPX, while the expression of the autophagy marker gene LC3B did not change (p < 0.05). After 7 d of fasting, the content of the ROS, the activity of SOD and GR, and the GSH content reached the maximum (p < 0.05). Concurrently, there was a significant rise in the quantity of autophagosomes. An RT-qPCR analysis revealed that seven d of starvation significantly elevated the mRNA expression of genes associated with the initiation and expansion of autophagosome membranes, vesicle recycling, and cargo recruitment, including ULK1, BECLIN1, LC3B, ATG3, ATG4B, ATG4C, ATG5, ATG9, and P62. After feeding resumed for 3 d, the mRNA level of BECLIN1, ATG3, ATG4B, ATG4C, ATG5, LC3B, and P62 still remained at a high level. The LC3II protein reached its highest level. All autophagy-related gene expression decreased in the 7-day resumed feeding group. Our data implied that short-term fasting can cause oxidative stress and disrupt the antioxidant system first and then induce autophagy in the muscles of rice flower carp. These findings shed light on how fasting affects muscle homeostasis in fish. ROS-induced autophagy of the skeletal muscle may confer the resistance of rice flower carp to short-term fasting. Full article

(This article belongs to the Special Issue Fisheries and Aquaculture Gene Expression)

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15 pages, 3252 KiB

Open AccessEditor’s ChoiceArticle

Dynamic Alternative Polyadenylation during Litopenaeus Vannamei Metamorphosis Development

by Xueqin Yang, Xiuli Chen, Chengzhang Liu, Zezhong Wang, Wei Lei, Qiangyong Li, Yongzhen Zhao and Xia Wang

Genes 2024, 15(7), 837; https://doi.org/10.3390/genes15070837 - 26 Jun 2024

Viewed by 2404

Abstract

As an important mechanism in the post-transcriptional regulation of eukaryotic gene expression, alternative polyadenylation (APA) plays a key role in biological processes such as cell proliferation and differentiation. However, the role and dynamic pattern of APA during Litopenaeus vannamei metamorphosis are poorly understood. [...] Read more.

As an important mechanism in the post-transcriptional regulation of eukaryotic gene expression, alternative polyadenylation (APA) plays a key role in biological processes such as cell proliferation and differentiation. However, the role and dynamic pattern of APA during Litopenaeus vannamei metamorphosis are poorly understood. Here, RNA-seq data covering from the embryo to the maturation (16 time points) of L. vannamei were utilized. We identified 247 differentially expressed APA events between early and adult stages, and through fuzzy mean clustering analysis, we discovered five dynamic APA patterns. Among them, the gradual elongation of the 3′UTR is the major APA pattern that changes over time, and its genes are enriched in the pathways of protein and energy metabolism. Finally, we constructed mRNA-miRNA and PPI networks and detected several central miRNAs that may regulate L. vannamei development. Our results revealed the complex APA mechanisms in L. vannamei metamorphosis, shedding new light on post-transcriptional regulation of crustacean metamorphosis. Full article

(This article belongs to the Special Issue Advances in Genes and Genomics of Aquatic Animals and Pathogens)

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20 pages, 6848 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of Chloroplast Genomes in Cephaleuros and Its Related Genus (Trentepohlia): Insights into Adaptive Evolution

by Jiao Fang, Lingling Zheng, Guoxiang Liu and Huan Zhu

Genes 2024, 15(7), 839; https://doi.org/10.3390/genes15070839 - 26 Jun 2024

Cited by 3 | Viewed by 2040

Abstract

Cephaleuros species are well-known as plant pathogens that cause red rust or algae spot diseases in many economically cultivated plants that grow in shady and humid environments. Despite their prevalence, the adaptive evolution of these pathogens remains poorly understood. We sequenced and characterized [...] Read more.

Cephaleuros species are well-known as plant pathogens that cause red rust or algae spot diseases in many economically cultivated plants that grow in shady and humid environments. Despite their prevalence, the adaptive evolution of these pathogens remains poorly understood. We sequenced and characterized three Cephaleuros (Cephaleuros lagerheimii, Cephaleuros diffusus, and Cephaleuros virescens) chloroplast genomes, and compared them with seven previously reported chloroplast genomes. The chloroplast sequences of C. lagerheimii, C. diffusus, and C. virescens were 480,613 bp, 383,846 bp, and 472,444 bp in length, respectively. These chloroplast genomes encoded 94 genes, including 27 tRNA genes, 3 rRNA genes, and 64 protein-coding genes. Comparative analysis uncovered that the variation in genome size was principally due to the length of intergenic spacer sequences, followed by introns. Furthermore, several highly variable regions (trnY-GTA, trnL-TAG, petA, psbT, trnD-GTC, trnL-TAA, ccsA, petG, psaA, psaB, rps11, rps2, and rps14) were identified. Codon bias analysis revealed that the codon usage pattern of Cephaleuros is predominantly shaped by natural selection. Additionally, six chloroplast protein-coding genes (atpF, chlN, psaA, psaB, psbA, and rbcL) were determined to be under positive selection, suggesting they may play a vital roles in the adaptation of Cephaleuros to low-light intensity habitats. Full article

(This article belongs to the Special Issue Advances in Evolution of Plant Organelle Genome—2nd Edition)

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14 pages, 5069 KiB

Open AccessEditor’s ChoiceArticle

The First Three Mitochondrial Genomes for the Characterization of the Genus Egeirotrioza (Hemiptera: Triozidae) and Phylogenetic Implications

by Zhulidezi Aishan, Ze-Lu Mu, Zi-Cong Li, Xin-Yu Luo and Ning Huangfu

Genes 2024, 15(7), 842; https://doi.org/10.3390/genes15070842 - 26 Jun 2024

Cited by 1 | Viewed by 1574

Abstract

(1) Background: Mitochondrial genomes are important markers for the study of phylogenetics and systematics. Triozidae includes some primary pests of Populus euphratica. The phylogenetic relationships of this group remain controversial due to the lack of molecular data. (2) Methods: Mitochondria of Egeirotrioza [...] Read more.

(1) Background: Mitochondrial genomes are important markers for the study of phylogenetics and systematics. Triozidae includes some primary pests of Populus euphratica. The phylogenetic relationships of this group remain controversial due to the lack of molecular data. (2) Methods: Mitochondria of Egeirotrioza Boselli were sequenced and assembled. We analyzed the sequence length, nucleotide composition, and evolutionary rate of Triozidae, combined with the 13 published mitochondrial genomes. (3) Results: The evolutionary rate of protein-coding genes was as follows: ATP8 > ND6 > ND5 > ND2 > ND4 > ND4L > ND1 > ND3 > APT6 > CYTB > COX3 > COX2 > COX1. We reconstructed the phylogenetic relationships of Triozidae based on 16 triozid mitochondrial genomes (thirteen ingroups and three outgroups) using the maximum likelihood (ML) and Bayesian inference (BI) approaches. The phylogenetic analysis of the 16 Triozidae mitochondrial genomes showed that Egeirotrioza was closely related to Leptynoptera. (4) Conclusions: We have identified 13 PCGs, 22 tRNAs, 2 rRNAs, and 1 control region (CR) of all newly sequenced mitochondrial genomes, which were the mitochondrial gene type in animals. The results of this study provide valuable genomic information for the study of psyllid species. Full article

(This article belongs to the Special Issue Genetics, Phylogeny, and Evolution of Insects)

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13 pages, 2207 KiB

Open AccessEditor’s ChoiceArticle

AMPK Deficiency Increases DNA Methylation and Aggravates Colorectal Tumorigenesis in AOM/DSS Mice

by Qi Sun, Qiyu Tian, Alejandro Bravo Iniguez, Xiaofei Sun, Hui Zhang, Jeanene Deavila, Min Du and Mei-Jun Zhu

Genes 2024, 15(7), 835; https://doi.org/10.3390/genes15070835 - 25 Jun 2024

Cited by 1 | Viewed by 2064

Abstract

The incidence of colorectal cancer (CRC) is closely linked to metabolic diseases. Accumulating evidence suggests the regulatory role of AMP-activated protein kinase (AMPK) in cancer metabolic reprogramming. In this study, wild-type and AMPK knockout mice were subjected to azoxymethane-induced and dextran sulfate sodium [...] Read more.

The incidence of colorectal cancer (CRC) is closely linked to metabolic diseases. Accumulating evidence suggests the regulatory role of AMP-activated protein kinase (AMPK) in cancer metabolic reprogramming. In this study, wild-type and AMPK knockout mice were subjected to azoxymethane-induced and dextran sulfate sodium (AOM/DSS)-promoted colitis-associated CRC induction. A stable AMPK-deficient Caco-2 cell line was also established for the mechanistic studies. The data showed that AMPK deficiency accelerated CRC development, characterized by increased tumor number, tumor size, and hyperplasia in AOM/DSS-treated mice. The aggravated colorectal tumorigenesis resulting from AMPK ablation was associated with reduced α-ketoglutarate production and ten-eleven translocation hydroxylase 2 (TET2) transcription, correlated with the reduced mismatch repair protein mutL homolog 1 (MLH1) protein. Furthermore, in AMPK-deficient Caco-2 cells, the mRNA expression of mismatch repair and tumor suppressor genes, intracellular α-ketoglutarate, and the protein level of TET2 were also downregulated. AMPK deficiency also increased hypermethylation in the CpG islands of Mlh1 in both colonic tissues and Caco-2 cells. In conclusion, AMPK deficiency leads to reduced α-ketoglutarate concentration and elevates the suppressive epigenetic modifications of tumor suppressor genes in gut epithelial cells, thereby increasing the risk of colorectal tumorigenesis. Given the modifiable nature of AMPK activity, it holds promise as a prospective molecular target for the prevention and treatment of CRC. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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15 pages, 7641 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification of the Whirly Gene Family and Its Potential Function in Low Phosphate Stress in Soybean (Glycine max)

by Zhimin Li, Xuhao Zhai, Lina Zhang, Yifei Yang, Hongqing Zhu, Haiyan Lü, Erhui Xiong, Shanshan Chu, Xingguo Zhang, Dan Zhang and Dandan Hu

Genes 2024, 15(7), 833; https://doi.org/10.3390/genes15070833 - 25 Jun 2024

Cited by 2 | Viewed by 1373

Abstract

The Whirly (WHY) gene family, functioning as transcription factors, plays an essential role in the regulation of plant metabolic responses, which has been demonstrated across multiple species. However, the WHY gene family and its functions in soybean remains unclear. In this [...] Read more.

The Whirly (WHY) gene family, functioning as transcription factors, plays an essential role in the regulation of plant metabolic responses, which has been demonstrated across multiple species. However, the WHY gene family and its functions in soybean remains unclear. In this paper, we conducted genome-wide screening and identification to characterize the WHY gene family. Seven WHY members were identified and randomly distributed across six chromosomes. The phylogenetic evolutionary tree of WHY genes in soybean and other species was divided into five clades. An in-depth analysis revealed that segmental duplications significantly contributed to the expansion of GmWHYs, and the GmWHY gene members may have experienced evolutionary pressure for purifying selection in soybeans. The analysis of promoter Cis-elements in GmWHYs suggested their potential significance in addressing diverse stress conditions. The expression patterns of GmWHYs exhibited tissue-specific variations throughout the different stages of soybean development. Additionally, six GmWHY genes exhibited different responses to low phosphate stress. These findings will provide a theoretical basis and valuable reference for the future exploration of WHY gene function. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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10 pages, 1362 KiB

Open AccessEditor’s ChoiceArticle

From Alpha-Thalassemia Trait to NPRL3-Related Epilepsy: A Genomic Diagnostic Odyssey

by Maryam Nabavi Nouri, Lama Alandijani, Kalene van Engelen, Soumitra Tole, Emilie Lalonde and Tugce B. Balci

Genes 2024, 15(7), 836; https://doi.org/10.3390/genes15070836 - 25 Jun 2024

Viewed by 2120

Abstract

Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates the mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, NPRL3 is situated near the α-globin gene cluster. Haploinsufficiency of NPRL3, either by [...] Read more.

Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates the mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, NPRL3 is situated near the α-globin gene cluster. Haploinsufficiency of NPRL3, either by deletion or a pathogenic variant, is associated with a variable phenotype of focal epilepsy, with or without malformations of cortical development, with known decreased penetrance. Case Description: This work details the diagnostic odyssey of a neurotypical 10-year-old boy who presented at age 2 with unusual nocturnal episodes and a history of microcytic anemia, as well as a review of the existing literature on NPRL3-related epilepsy, with an emphasis on individuals with deletions who also present with α-thalassemia trait. The proband’s episodes were mistaken for gastroesophageal reflux disease for several years. He had molecular testing for his α-thalassemia trait and was noted to carry a deletion encompassing the regulatory region of the α-thalassemia gene cluster. Following the onset of overt focal motor seizures, genetic testing revealed a heterozygous loss of NPRL3, within a 106 kb microdeletion on chromosome 16p13.3, inherited from his mother. This deletion encompassed the entire NPRL3 gene, which overlaps the regulatory region of the α-globin gene cluster, giving him the dual diagnosis of NPRL3-related epilepsy and α-thalassemia trait. Brain imaging postprocessing showed left hippocampal sclerosis and mid-posterior para-hippocampal focal cortical dysplasia, leading to the consideration of epilepsy surgery. Conclusions: This case underscores the necessity of early and comprehensive genetic assessments in children with epilepsy accompanied by systemic features, even in the absence of a family history of epilepsy or a developmental delay. Recognizing phenotypic overlaps is crucial to avoid diagnostic delays. Our findings also highlight the impact of disruptions in regulatory regions in genetic disorders: any individual with full gene deletion of NPRL3 would have, at a minimum, α-thalassemia trait, due to the presence of the major regulatory element of α-globin genes overlapping the gene’s introns. Full article

(This article belongs to the Special Issue Impact of Genetic Testing in Epilepsy and Other Neurological Conditions)

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21 pages, 3610 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Protein Assemblies in Translesion Synthesis

by Gianluca A. Arianna and Dmitry M. Korzhnev

Genes 2024, 15(7), 832; https://doi.org/10.3390/genes15070832 - 24 Jun 2024

Cited by 2 | Viewed by 2153

Abstract

Translesion synthesis (TLS) is a mechanism of DNA damage tolerance utilized by eukaryotic cells to replicate DNA across lesions that impede the high-fidelity replication machinery. In TLS, a series of specialized DNA polymerases are employed, which recognize specific DNA lesions, insert nucleotides across [...] Read more.

Translesion synthesis (TLS) is a mechanism of DNA damage tolerance utilized by eukaryotic cells to replicate DNA across lesions that impede the high-fidelity replication machinery. In TLS, a series of specialized DNA polymerases are employed, which recognize specific DNA lesions, insert nucleotides across the damage, and extend the distorted primer-template. This allows cells to preserve genetic integrity at the cost of mutations. In humans, TLS enzymes include the Y-family, inserter polymerases, Polη, Polι, Polκ, Rev1, and the B-family extender polymerase Polζ, while in S. cerevisiae only Polη, Rev1, and Polζ are present. To bypass DNA lesions, TLS polymerases cooperate, assembling into a complex on the eukaryotic sliding clamp, PCNA, termed the TLS mutasome. The mutasome assembly is contingent on protein–protein interactions (PPIs) between the modular domains and subunits of TLS enzymes, and their interactions with PCNA and DNA. While the structural mechanisms of DNA lesion bypass by the TLS polymerases and PPIs of their individual modules are well understood, the mechanisms by which they cooperate in the context of TLS complexes have remained elusive. This review focuses on structural studies of TLS polymerases and describes the case of TLS holoenzyme assemblies in action emerging from recent high-resolution Cryo-EM studies. Full article

(This article belongs to the Special Issue DNA Damage and Repair in Microorganisms, Plants and Mammalian Systems)

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12 pages, 3209 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Insights into the Developmental Dynamics of Eimeria acervulina: A Comparative Study of a Precocious Line and the Wild Type

by Ning Zhang, Xiaojin Li, Jie Liu, Linlin Chen, Sixin Zhang, Xianyong Liu, Xinming Tang, Xun Suo and Yuanyuan Zhang

Genes 2024, 15(7), 831; https://doi.org/10.3390/genes15070831 - 24 Jun 2024

Cited by 1 | Viewed by 1227

Abstract

Coccidiosis, a parasitic disease caused by single or multiple Eimeria species, leads to significant economic losses in the poultry industry. The Eimeria life cycle includes schizogony, gametogony, and sporogony. To investigate the dynamics of gene expression and regulatory networks during the development of [...] Read more.

Coccidiosis, a parasitic disease caused by single or multiple Eimeria species, leads to significant economic losses in the poultry industry. The Eimeria life cycle includes schizogony, gametogony, and sporogony. To investigate the dynamics of gene expression and regulatory networks during the development of Eimeria acervulina, we employed time-course transcriptomics to rigorously compare the gene expression patterns between a precocious line (PL) and the wild type (WT) of E. acervulina. The results revealed that the PL enters into gametogony 12 h earlier than the WT, and both the PL and WT exhibited distinct clustering patterns during the development phase. A weighted gene co-expression network analysis (WGCNA) identified genes specifically expressed at four distinct developmental stages, schizogony, gametogony, sporulated oocysts, and unsporulated oocysts, clarifying the key biological processes at each stage. This study used global transcriptome profiling to elucidate molecular variations throughout the E. acervulina life cycle, providing critical insights into molecular characterization and valuable resources for investigating other apicomplexan parasites of public health importance. Full article

(This article belongs to the Special Issue Feature Papers in Microbial Genetics in 2024)

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11 pages, 5481 KiB

Open AccessEditor’s ChoiceArticle

Complete Mitochondrial Genome and Phylogenetic Analysis of the Blue Whistling Thrush (Myophonus caeruleus)

by Zhenfeng Yuan, Peng Liu, Xi Lu, Dong Zhu, Jun Liu, Qiang Guo, Wenping Zhang and Yubao Duan

Genes 2024, 15(7), 830; https://doi.org/10.3390/genes15070830 - 24 Jun 2024

Cited by 2 | Viewed by 1448

Abstract

The blue whistling thrush (Myophonus caeruleus) is a bird belonging to the order Passeriformes and family Muscicapidae. M. caeruleus is widely distributed in China, Pakistan, India, and Myanmar and is a resident bird in the southern part of the Yangtze River [...] Read more.

The blue whistling thrush (Myophonus caeruleus) is a bird belonging to the order Passeriformes and family Muscicapidae. M. caeruleus is widely distributed in China, Pakistan, India, and Myanmar and is a resident bird in the southern part of the Yangtze River in China and summer migratory bird in the northern part of the Yangtze River. At present, there are some controversies about the classification of M. caeruleus. We use complete mitochondrial genomes to provide insights into the phylogenetic position of M. caeruleus and its relationships among Muscicapidae. The mitochondrial genome (GenBank: MN564936) is 16,815 bp long and contains 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and a non-coding control region (D-loop). The thirteen PCGs started with GTG and ATG and ended with five types of stop codons. The nucleotide composition of T was 23.71%, that of C was 31.45%, that of A was 30.06%, and that of G was 14.78%. The secondary structures of 22 tRNAs were predicted, all of which could form typical cloverleaf structures. There were 24 mismatches, mainly G–U mismatches. Through phylogenetic tree reconstruction, it was found that Saxicola, Monticola, Oenanthe, and Phoenicurus were clustered into one clade, together with the sister group of Myophonus. Full article

(This article belongs to the Special Issue Wildlife Genetic Diversity and Genomics)

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20 pages, 3122 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Mustn1 in Skeletal Muscle: A Novel Regulator?

by Charles J. Kim and Michael Hadjiargyrou

Genes 2024, 15(7), 829; https://doi.org/10.3390/genes15070829 - 23 Jun 2024

Cited by 3 | Viewed by 2268

Abstract

Skeletal muscle is a complex organ essential for locomotion, posture, and metabolic health. This review explores our current knowledge of Mustn1, particularly in the development and function of skeletal muscle. Mustn1 expression originates from Pax7-positive satellite cells in skeletal muscle, peaks during [...] Read more.

Skeletal muscle is a complex organ essential for locomotion, posture, and metabolic health. This review explores our current knowledge of Mustn1, particularly in the development and function of skeletal muscle. Mustn1 expression originates from Pax7-positive satellite cells in skeletal muscle, peaks during around the third postnatal month, and is crucial for muscle fiber differentiation, fusion, growth, and regeneration. Clinically, Mustn1 expression is potentially linked to muscle-wasting conditions such as muscular dystrophies. Studies have illustrated that Mustn1 responds dynamically to injury and exercise. Notably, ablation of Mustn1 in skeletal muscle affects a broad spectrum of physiological aspects, including glucose metabolism, grip strength, gait, peak contractile strength, and myofiber composition. This review summarizes our current knowledge of Mustn1’s role in skeletal muscle and proposes future research directions, with a goal of elucidating the molecular function of this regulatory gene. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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15 pages, 4195 KiB

Open AccessEditor’s ChoiceArticle

De Novo Pathogenic Variant in FBRSL1, Non OMIM Gene Paralogue AUTS2, Causes a Novel Recognizable Syndromic Manifestation with Intellectual Disability; An Additional Patient and Review of the Literature

by Nenad Bukvic, Marta De Rinaldis, Massimiliano Chetta, Antonio Trabacca, Maria Teresa Bassi, René Massimiliano Marsano, Lenka Holoubkova, Maria Rivieccio, Maria Oro, Nicoletta Resta, Jennifer Kerkhof, Bekim Sadikovic and Luigi Viggiano

Genes 2024, 15(7), 826; https://doi.org/10.3390/genes15070826 - 22 Jun 2024

Cited by 1 | Viewed by 2215

Abstract

FBRSL1, together with FBRS and AUTS2 (Activator of Transcription and Developmental Regulator; OMIM 607270), constitutes a tripartite AUTS2 gene family. AUTS2 and FBRSL1 are evolutionarily more closely related to each other than to FBRS (Fibrosin 1; OMIM 608601). [...] Read more.

FBRSL1, together with FBRS and AUTS2 (Activator of Transcription and Developmental Regulator; OMIM 607270), constitutes a tripartite AUTS2 gene family. AUTS2 and FBRSL1 are evolutionarily more closely related to each other than to FBRS (Fibrosin 1; OMIM 608601). Despite its paralogous relation to AUTS2, FBRSL1’s precise role remains unclear, though it likely shares functions in neurogenesis and transcriptional regulation. Herein, we report the clinical presentation with therapeutic approaches and the molecular etiology of a patient harboring a de novo truncating variant (c.371dupC) in FBRSL1, leading to a premature stop codon (p.Cys125Leufs*7). Our study extends previous knowledge by highlighting potential interactions and implications of this variant, alongside maternal and paternal duplications, for the patient’s phenotype. Using sequence conservation data and in silico analysis of the truncated protein, we generated a predicted domain structure. Furthermore, our in silico analysis was extended by taking into account SNP array results. The extension of in silico analysis was performed due to the possibility that the coexistence of FBRSL1 truncating variant contemporary with maternal and paternal duplication could be a modifier of proband’s phenotype and/or influence the novel syndrome clinical characteristics. FBRSL1 protein may be involved in neurodevelopment due to its homology with AUTS2, together with distinctive neuronal expression profiles, and thus should be considered as a potential modulation of clinical characteristics in a novel syndrome. Finally, considering that FBRSL1 is apparently involved in neurogenesis and in transcriptional regulatory networks that orchestrate gene expression, together with the observation that different genetic syndromes are associated with distinct genomic DNA methylation patterns, the specific episignature has been explored. Full article

(This article belongs to the Special Issue Molecular Basis and Genetics of Intellectual Disability)

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17 pages, 4540 KiB

Open AccessEditor’s ChoiceArticle

Identification of Wheat Glutamate Synthetase Gene Family and Expression Analysis under Nitrogen Stress

by Songshuo Li, Bo Jiao, Jiao Wang, Pu Zhao, Fushuang Dong, Fan Yang, Chunhong Ma, Peng Guo and Shuo Zhou

Genes 2024, 15(7), 827; https://doi.org/10.3390/genes15070827 - 22 Jun 2024

Cited by 1 | Viewed by 1933

Abstract

Nitrogen (N), as the main component of biological macromolecules, maintains the basic process of plant growth and development. GOGAT, as a key enzyme in the N assimilation process, catalyzes α-ketoglutaric acid and glutamine to form glutamate. In this study, six GOGAT genes in [...] Read more.

Nitrogen (N), as the main component of biological macromolecules, maintains the basic process of plant growth and development. GOGAT, as a key enzyme in the N assimilation process, catalyzes α-ketoglutaric acid and glutamine to form glutamate. In this study, six GOGAT genes in wheat (Triticum aestivum L.) were identified and classified into two subfamilies, Fd-GOGAT (TaGOGAT2s) and NADH-GOGAT (TaGOGAT3s), according to the type of electron donor. Subcellular localization prediction showed that TaGOGAT3-D was localized in mitochondria and that the other five TaGOGATs were localized in chloroplasts. Via the analysis of promoter elements, many binding sites related to growth and development, hormone regulation and plant stress resistance regulations were found on the TaGOGAT promoters. The tissue-specificity expression analysis showed that TaGOGAT2s were mainly expressed in wheat leaves and flag leaves, while TaGOGAT3s were highly expressed in roots and leaves. The expression level of TaGOGATs and the enzyme activity of TaGOGAT3s in the leaves and roots of wheat seedlings were influenced by the treatment of N deficiency. This study conducted a systematic analysis of wheat GOGAT genes, providing a theoretical basis not only for the functional analysis of TaGOGATs, but also for the study of wheat nitrogen use efficiency (NUE). Full article

(This article belongs to the Special Issue Breeding and Genetics in Wheat)

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26 pages, 4586 KiB

Open AccessEditor’s ChoiceArticle

Combined Metabolomics and Transcriptomics Analysis of the Distribution of Flavonoids in the Fibrous Root and Taproot of Polygonatum kingianum Coll.et Hemsl

by Xinchun Mo, Ling Wang, Chenghua Yu and Can Kou

Genes 2024, 15(7), 828; https://doi.org/10.3390/genes15070828 - 22 Jun 2024

Cited by 1 | Viewed by 1756

Abstract

Polygonati rhizoma, known for its distinct yellow rhizomes, is a common therapeutic and culinary plant in Far East Asia. The hue of medicinal plants is closely tied to the flavonoid biosynthesis and content levels. In this research, the fibrous root and taproot of [...] Read more.

Polygonati rhizoma, known for its distinct yellow rhizomes, is a common therapeutic and culinary plant in Far East Asia. The hue of medicinal plants is closely tied to the flavonoid biosynthesis and content levels. In this research, the fibrous root and taproot of Polygonatum kingianum Coll.et Hemsl. were studied to explore the secondary metabolite expression and flavonoid biosynthesis mechanisms using transcriptomics and metabolomics. Metabolic analysis identified that the differentially accumulated metabolites (DAMs) in the fibrous root and taproot were predominantly flavonoids, steroids, alkaloids, and phenolic acids. Overall, 200 flavonoids were identified in P. kingianum Coll.et Hemsl., with 170 exhibiting variances between the fibrous root and taproot. The transcriptome analysis revealed that a total of 289 unigenes encoding 32 enzymes were annotated into four flavonoid biosynthesis pathways, which include phenylpropanoid biosynthesis pathway, flavonoid biosynthesis pathway, isoflavonoid biosynthesis pathway, and flavone and flavonol biosynthesis pathway. The integration of transcriptomic and metabolomic data elucidated that the 76 differentially expressed genes (DEGs) encoding 13 enzyme genes (HCT, CCOMT, C4H, C3′H, CHI, PGT1, FLS, F3′H, CHS, ANR, DFR, F3′5′H, and LAR) and 15 DAMs preferred to be regulated in the flavonoid biosynthesis pathway. The expression of 10 DEGs was validated by qRT-PCR, agreeing with the same results by RNA-Seq. These findings shed light into the biosynthesis of secondary metabolites in P. kingianum Coll.et Hemsl., offering valuable information for the sustainable utilization and enhancement of this plant species. Full article

(This article belongs to the Special Issue 5Gs in Crop Genetic and Genomic Improvement: 2nd Edition)

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12 pages, 1849 KiB

Open AccessEditor’s ChoiceBrief Report

Advanced Analysis and Validation of a microRNA Signature for Fanconi Anemia

by Enrico Cappelli, Silvia Ravera, Nadia Bertola, Federica Grilli, Margherita Squillario, Stefano Regis and Paolo Degan

Genes 2024, 15(7), 820; https://doi.org/10.3390/genes15070820 - 21 Jun 2024

Cited by 1 | Viewed by 1441

Abstract

Some years ago, we reported the generation of a Fanconi anemia (FA) microRNA signature. This study aims to develop an analytical strategy to select a smaller and more reliable set of molecules that could be tested for potential benefits for the FA phenotype, [...] Read more.

Some years ago, we reported the generation of a Fanconi anemia (FA) microRNA signature. This study aims to develop an analytical strategy to select a smaller and more reliable set of molecules that could be tested for potential benefits for the FA phenotype, elucidate its biochemical and molecular mechanisms, address experimental activity, and evaluate its possible impact on FA therapy. In silico analyses of the data obtained in the original study were thoroughly processed and anenrichment analysis was employed to identify the classes of genes that are over-represented in the FA-miRNA population under study. Primary bone marrow mononuclear cells (MNCs) from sixFA patients and sixhealthy donors as control samples were employed in the study. RNAs containing the small RNA fractions were reverse-transcribed and real-time PCR was performed in triplicate using the specific primers. Experiments were performed in triplicate.The in-silico analysis reported six miRNAs as likely contributors to the complex pathological spectrum of FA. Among these, three miRNAs were validated by real-time PCR. Primary bone marrow mononuclear cells (MNCs) reported a significant reduction in the expression level of miRNA-1246 and miRNA-206 in the FA samples in comparison to controls.This study highlights several biochemical pathways as culprits in the phenotypic manifestations and the pathophysiological mechanisms acting in FA. A relatively low number of miRNAs appear involved in all these different phenotypes, demonstrating the extreme plasticity of the gene expression modulation. This study further highlights miR-206 as a pivotal player in regulatory functions and signaling in the bone marrow mesenchymal stem cell (BMSC) process in FA. Due to this evidence, the activity of miR-206 in FA deserves specific experimental scrutiny. The results, here presented, might be relevant in the management of FA. Full article

(This article belongs to the Section RNA)

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12 pages, 567 KiB

Open AccessEditor’s ChoiceReview

Preparing for Patient-Customized N-of-1 Antisense Oligonucleotide Therapy to Treat Rare Diseases

by Harry Wilton-Clark, Eric Yan and Toshifumi Yokota

Genes 2024, 15(7), 821; https://doi.org/10.3390/genes15070821 - 21 Jun 2024

Cited by 7 | Viewed by 4631

Abstract

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of [...] Read more.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development and addresses some of the major limitations that previously hindered the development of therapies for rare diseases. Full article

(This article belongs to the Special Issue Molecular Genetics of Neurodegenerative Diseases and Neuromuscular Diseases)

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16 pages, 4773 KiB

Open AccessEditor’s ChoiceArticle

Identification and Comprehensive Analysis of OFP Genes for Fruit Shape Influence in Mango

by Qiuping Wu, Rui Xia, Jie Yang, Rong Chen, Zaohai Zeng and Chao Fan

Genes 2024, 15(7), 823; https://doi.org/10.3390/genes15070823 - 21 Jun 2024

Cited by 1 | Viewed by 1375

Abstract

OVATE family proteins (OFPs) are a class of plant-specific proteins with a conserved OVATE domain that play fundamental roles in fruit development and plant growth. Mango (Mangifera indica L.) is an economically important subtropical fruit tree characterized by a diverse array of [...] Read more.

OVATE family proteins (OFPs) are a class of plant-specific proteins with a conserved OVATE domain that play fundamental roles in fruit development and plant growth. Mango (Mangifera indica L.) is an economically important subtropical fruit tree characterized by a diverse array of fruit shapes and sizes. Despite extensive research on OFPs across various species, there remains a scarcity of information regarding OFPs in mango. Here, we have successfully identified 25 OFP genes (MiOFPs) in mango, each of which exhibits the conserved OVATE domains. The MiOFP gene exhibit a range of 2–6 motifs, with all genes containing both motif 1 and motif 2. Phylogenetic analysis on 97 OFPs (including 18 AtOFPs, 24 SlOFPs, 25 MiOFPs, and 30 OsOFPs) indicated that MiOFPs could be divided into three main clades: clade I, II, and III. Comparative morphological analysis identified significant variations in fruit longitudinal diameter, fruit transverse diameter, and fruit shape index between two distinct shaped mango cultivars (‘Hongxiangya’ and ‘Jingpingmang’) at DAP5, DAP7, and DAP10 stages. The subsequent examination of paraffin sections revealed distinct patterns of cell elongation. The majority of MiOFP genes exhibited predominantly expressed in developing organs, specifically flowers and immature fruits, while displaying distinct expression patterns. RNA-Seq analysis revealed significant disparities in the expression levels of several OFP genes, including MiOFP5, MiOFP11, MiOFP21, MiOFP22, MiOFP23, and MiOFP25, between the two mango cultivars. These findings suggest that these six genes may play a crucial role for fruit shape in mango, especially the MiOFP22. The findings of this study have established a basis for future investigations into MiOFPs in mango, offering a solid foundation for further research in this field. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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18 pages, 4339 KiB

Open AccessEditor’s ChoiceArticle

Soil Microbial Communities in Lemon Orchards Affected by Citrus Mal Secco Disease

by Alexandros Mosca, Giulio Dimaria, Daniele Nicotra, Francesco Modica, Maria Elena Massimino, Antonino F. Catara, Giuseppe Scuderi, Marcella Russo and Vittoria Catara

Genes 2024, 15(7), 824; https://doi.org/10.3390/genes15070824 - 21 Jun 2024

Viewed by 2116

Abstract

Mal secco is a vascular disease of citrus caused by the mitosporic fungus Plenodomus tracheiphilus. Soil containing infected plant material constitutes an inoculum source for root infections. In this study, the soil bacterial and fungal communities of five lemon orchards located in [...] Read more.

Mal secco is a vascular disease of citrus caused by the mitosporic fungus Plenodomus tracheiphilus. Soil containing infected plant material constitutes an inoculum source for root infections. In this study, the soil bacterial and fungal communities of five lemon orchards located in Syracuse Province (Sicily, Italy) affected by mal secco were analyzed. Soil samples were collected under lemon tree canopies and subjected to total genomic DNA extraction. The fungal DNA was detected through qPCR in all orchards, with variable concentrations. Bacterial and fungal communities were profiled using 16S and ITS amplicon-based high-throughput sequencing, respectively. According to our results, the relative abundances of the most represented bacterial phyla (e.g., Proteobacteria, Actinobacteriota, Acidobacteriota) changed across the orchards, while in the fungal community, the phylum Ascomycota was dominant, with Basidiomycota and Mortierellomycota abundances fluctuating. On the whole, β diversity analysis showed significant variation in the composition of the soil microbial communities across the orchards. This result was confirmed by the analysis of the core community (taxa present at ≥ 75% of total samples), where putative beneficial bacteria resulted in significantly enriched fungus-infected soil samples, suggesting complex microbial interactions. Our findings shed light on the composition and diversity of the soil microbiome in lemon orchards with the occurrence of mal secco infections. Full article

(This article belongs to the Special Issue Microbiome Analysis Techniques and Discovery)

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15 pages, 4506 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome Analysis Reveals the Molecular Mechanism of the Leaf Yellowing in Allotriploid Cucumber

by Han Wang, Lei Xia, Jinfeng Chen and Chunyan Cheng

Genes 2024, 15(7), 825; https://doi.org/10.3390/genes15070825 - 21 Jun 2024

Cited by 1 | Viewed by 1643

Abstract

Yellowing leaves are ideal materials for studying the metabolic pathways of photosynthetic pigment chloroplast development, and the mechanism of photosynthetic systems. Here, we obtained a triploid material HCC (2n = 3x = 26), which was derived from hybridization between the artificial tetraploid Cucumis [...] Read more.

Yellowing leaves are ideal materials for studying the metabolic pathways of photosynthetic pigment chloroplast development, and the mechanism of photosynthetic systems. Here, we obtained a triploid material HCC (2n = 3x = 26), which was derived from hybridization between the artificial tetraploid Cucumis × hytivus (2n = 4x = 38, HHCC) and the cultivated cucumber Cucumis sativus (2n = 2x = 14, CC), and this triploid HCC showed obvious leaf yellowing characteristics. Phenotypic observation results showed that chloroplast development was impaired, the chlorophyll content decreased, and photosynthesis decreased in yellowing HCC leaves. The transcriptome results indicated that HCC-GLK is significantly downregulated in HCC and participates in the regulation of leaf yellowing. GO enrichment analysis revealed that differential genes were enriched in the heme binding and tetrapyrrole binding pathways related to leaf color. KEGG enrichment analysis revealed that differential genes were predominantly enriched in photosynthesis-related pathways. The experimental results of VIGS and yeast hybridization showed that silencing the GLK gene can induce leaf yellowing in cucumber plants, and the GLK protein can affect plant chloroplast development by interacting with the CAB3C protein (light-harvesting chlorophyll a/b binding) in the plant chlorophyll synthesis pathway. The current findings have not only enhanced our understanding of the regulatory mechanism of the GLK transcription factor in cucumber but also introduced novel insights and directions for investigating the molecular mechanism underlying polyploid leaf yellowing. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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